Cov tshuaj ntawm cov tshuaj insulin degludec insulin aspart * (insulin degludec insulin aspart *)
Cov nplooj ntawv no muab cov npe ntawm tag nrho cov Insugen-30/70 analogues (Bifazik) los ntawm cov lus qhia thiab kev qhia txog kev siv. Cov npe ntawm cov pheej yig analogues, thiab koj kuj tuaj yeem sib piv cov nqi hauv cov khw muag tshuaj.
- Cov khoom pheej yig tshaj ntawm Cov Insugen-30/70 (Bifazik):Neej Neeg Sib
- Tus qauv nrov tshaj plaws ntawm Insugen-30/70 (Bifazik):Neej Neeg Sib
- Kev faib tawm ATX: Cov tshuaj insulin (tib neeg)
- Cov khoom xyaw nquag / muaj pes tsawg leeg: tib neeg cov insulin
| # | Npe | Nqe hauv Lavxias | Nqe hauv Ukraine |
|---|---|---|---|
| 1 | Neej Neeg Sib tshuaj insulin lispro Analogue hauv kev taw qhia thiab txoj kev siv | 57 rub | 221 UAH |
| 2 | Humulin M3 tib neeg cov insulin Analogue nyob rau hauv muaj pes tsawg leeg thiab qhia tau | 212 RUB | -- |
| 3 | Ryzodeg Flextach tshuaj insulin aspart, insulin degludec Analogue hauv kev taw qhia thiab txoj kev siv | 6 699 tshiav | 2 UAH |
Thaum xam xyuas tus nqi pheej yig analogues Insugen-30/70 (Bifazik) tus nqi yam tsawg kawg nkaus uas tau pom hauv daim ntawv teev tus nqi muab los ntawm cov khw muag tshuaj tau raug coj los suav
| # | Npe | Nqe hauv Lavxias | Nqe hauv Ukraine |
|---|---|---|---|
| 1 | Neej Neeg Sib tshuaj insulin lispro Analogue hauv kev taw qhia thiab txoj kev siv | 57 rub | 221 UAH |
| 2 | Humulin M3 tib neeg cov insulin Analogue nyob rau hauv muaj pes tsawg leeg thiab qhia tau | 212 RUB | -- |
| 3 | Novomax Flekspen insulin aspart Analogue hauv kev taw qhia thiab txoj kev siv | -- | -- |
| 4 | Neej neeg k25 100r tib neeg cov insulin Analogue nyob rau hauv muaj pes tsawg leeg thiab qhia tau | -- | -- |
| 5 | Ryzodeg Flextach tshuaj insulin aspart, insulin degludec Analogue hauv kev taw qhia thiab txoj kev siv | 6 699 tshiav | 2 UAH |
Muab daim ntawv teev cov tshuaj analogues raws li kev txheeb cais ntawm cov tshuaj feem ntau thov
Analogs hauv kev muaj pes tsawg leeg thiab qhia txog kev siv
| Npe | Nqe hauv Lavxias | Nqe hauv Ukraine |
|---|---|---|
| Humodar k25 100r tib neeg cov insulin | -- | -- |
| Gensulin M30 tib neeg cov insulin | -- | 123 UAH |
| Insuman Comb insulin tib neeg | -- | 119 UAH |
| Mikstard tib neeg cov kua dej | -- | 116 UAH |
| Mixtard Penfill Insulin Tib Neeg | -- | -- |
| Farmasulin N 30/70 tib neeg cov tshuaj insulin | -- | 101 UAH |
| Tib neeg cov insulin Mulin | 212 RUB | -- |
Cov npe saum toj no ntawm cov yeeb tshuaj analogues, uas qhia hloov chaw Insugen-30/70 (Bifazik), yog qhov tsim nyog tshaj plaws vim tias lawv muaj tib cov tshuaj sib luag thiab sib luag ua ke raws li kev taw qhia rau kev siv
Analogs los ntawm qhov taw qhia thiab cov qauv ntawm kev siv
| Npe | Nqe hauv Lavxias | Nqe hauv Ukraine |
|---|---|---|
| Cov Pwm Ua Sib xyaw ua kua insulin lispro | 57 rub | 221 UAH |
| Novomax Flekspen insulin aspart | -- | -- |
| Ryzodeg Flextach insulin aspart, insulin degludec | 6 699 tshiav | 2 UAH |
Sib txawv muaj pes tsawg leeg, tuaj yeem ua ke nyob rau hauv kev taw qhia thiab cov qauv ntawm daim ntawv thov
| Npe | Nqe hauv Lavxias | Nqe hauv Ukraine |
|---|---|---|
| Cov tshuaj insulin | 178 RUB | 133 UAH |
| Actrapid | 35 txhuam | 115 UAH |
| Actrapid nm | 35 txhuam | 115 UAH |
| Actrapid nm mem tes | 469 rub | 115 UAH |
| Biosulin P | 175 rub | -- |
| Insuman Ceev Heev Tib Neeg Insulin | 1082 txhuam | 100 UAH |
| Humodar p100r tib neeg cov insulin | -- | -- |
| Tib neeg cov insulin tsis tu ncua | 28 RUB | 1133 UAH |
| Yawg Hlob | -- | 79 UAH |
| Gensulin P tib neeg cov tshuaj insulin | -- | 104 UAH |
| Insugen-R (Tsis tu ncua) tib neeg cov kua dej | -- | -- |
| Rinsulin P tib neeg cov tshuaj insulin | 433 plhaw | -- |
| Farmasulin N tib neeg cov tshuaj insulin | -- | 88 UAH |
| Tshuaj insulin Cov tib neeg cov tshuaj insulin | -- | 593 UAH |
| Monodar insulin (nqaij npuas) | -- | 80 UAH |
| Kev ntsuas cov tshuaj insulin lispro | 57 rub | 221 UAH |
| Lispro insulin recombinant Lispro | -- | -- |
| NovoRapid Flexpen Cwj mem Insulin Aspart | 28 RUB | 249 UAH |
| NovoRapid Penfill tshuaj insulin aspart | 1601 rub | 1643 UAH |
| Epidera Insulin Glulisin | -- | 146 UAH |
| Apidra SoloStar Glulisin | 1500 RUB | 2250 UAH |
| Biosulin N | 200 txhuam | -- |
| Insuman basal tib neeg insulin | 1170 RUB | 100 UAH |
| Protafan | 26 RUB | 116 UAH |
| Humodar b100r tib neeg cov insulin | -- | -- |
| Humulin nph tib neeg insulin | 166 RUB | 205 UAH |
| Gensulin N tib neeg cov insulin | -- | 123 UAH |
| Insugen-N (NPH) tib neeg cov tshuaj insulin | -- | -- |
| Protafan NM neeg insulin | 356 rub | 116 UAH |
| Protafan NM Penfill insulin tib neeg | 857 rub | 590 UAH |
| Rinsulin NPH tib neeg cov tshuaj insulin | 372 RUB | -- |
| Farmasulin N NP tib neeg cov kua dej | -- | 88 UAH |
| Cov Tshuaj Insulin Stabiliser Cov Tib Neeg Ua Reinbinant Insulin | -- | 692 UAH |
| Insulin-B Berlin-Chemie Insulin | -- | -- |
| Monodar B insulin (nqaij npuas) | -- | 80 UAH |
| Lantus insulin glargine | 45 rub | 250 UAH |
| Lantus SoloStar cov tshuaj insulin glargine | 45 rub | 250 UAH |
| Tujeo SoloStar cov tshuaj insulin glargine | 30 RUB | -- |
| Levemir Penfill cov tshuaj insulin | 167 tshiav | -- |
| Levemir Flexpen Cwj mem Insulin Detemir | 537 plhaw | 335 UAH |
| Tresiba Flextach Insulin Degludec | 5100 rub | 2 UAH |
Yuav ua li cas thiaj nrhiav tau qhov pheej yig tshuaj ntawm cov tshuaj kim?
Txhawm rau kom pom qhov pheej yig cov khoom sib piv rau cov tshuaj, cov dav dav lossis cov lus sau, ua ntej txhua yam peb pom zoo kom them sai sai rau qhov muaj pes tsawg leeg, uas yog rau tib cov tshuaj nquag thiab qhia tau rau kev siv. Cov tshuaj sib xyaw zoo ib yam ntawm cov tshuaj yuav qhia tau tias cov tshuaj cuam tshuam nrog cov tshuaj, kws tshuaj sib npaug lossis chaw muag tshuaj. Txawm li cas los xij, tsis txhob hnov qab txog qhov ua tsis muaj zog ntawm cov tshuaj uas zoo sib xws, uas tuaj yeem cuam tshuam kev nyab xeeb thiab ua haujlwm. Tsis txhob hnov qab txog cov lus qhia ntawm cov kws kho mob, kev noj tshuaj rau nws tus kheej tuaj yeem tsim kev puas tsuaj rau koj kev noj qab haus huv, yog li nco ntsoov sab laj nrog koj tus kws kho mob ua ntej siv cov tshuaj.
Qhia txog ntawm cov tshuaj
Cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) - Cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® Penfill ® yog kev sib xyaw ua ke muaj cov tshuaj tiv thaiv kab ke ntawm tib neeg insulin ultra-ntev ua yeeb yam (insulin degludec) thiab kev ua yeeb yam sai sai ntawm tib neeg insulin (insulin aspart) ua los ntawm cov thev naus laus zis ua kom muaj zog. DNA siv ib hom ntawm Saccharomyces cerevisiae.
Cov tshuaj insulin degludec thiab cov tshuaj insulin aspart hauv ib txoj hauv kev khi rau cov receptor ntawm tib neeg endogenous insulin thiab sib cuam tshuam nrog nws, paub lawv cov nyhuv pharmacological zoo ib yam li cov nyhuv ntawm tib neeg insulin. Qhov ua rau lub ntsej muag ntshav ntawm insulin yog vim muaj kev siv cov kua nplaum ntau ntxiv los ntawm cov ntaub so ntswg tom qab khi ntawm insulin rau cov leeg nqaij thiab cov cell rog, thiab tib lub sij hawm txo tus nqi ntawm cov piam thaj los ntawm lub siab.
Cov chaw muag tshuaj los ntawm cov tshuaj sib txawv ntawm cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) f Penfill ® muaj qhov sib txawv thiab cov ntawv qhia dav dav ntawm cov tshuaj cuam tshuam cov profiles ntawm kev txiav txim ntawm cov feem ntawm ib leeg: kev kub ceev insulin aspart thiab insulin degludec ntawm kev ncua ntev.
Lub hauv paus ua haujlwm ntawm cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® Penfill ®, uas muaj qhov kev ua haujlwm ntev ntev (insulin degludec), tom qab subcutaneous txhaj tshuaj tiv thaiv soluble multhexamers nyob rau hauv subcutaneous depot, los ntawm qhov muaj ib qho kev nruam qeeb ntawm insulin degludec rau hauv cov kev ncig. tiaj tiaj profile ntawm kev txiav txim thiab ruaj khov hypoglycemic nyhuv ntawm cov tshuaj. Cov nyhuv no tau muab khaws cia ua ke nrog insulin aspart thiab tsis cuam tshuam rau tus nqi ntawm kev nqus ntawm monomers ntawm kev ua yeeb yam sai li sai tau insulin aspart.
Cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® Penfill ® pib ua kom sai, muab qhov ua tau zoo rau insulin sai sai tom qab kev txhaj tshuaj, thaum lub hauv paus tiv thaiv muaj qhov tiaj, ruaj khov thiab qhov ntev ntev kev txiav txim siab profile uas muab qhov xav tau ntawm basal. nyob rau hauv insulin. Lub sijhawm ntawm kev ua ntawm ib koob nkaus xwb ntawm cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® Penfill ® ntau dua 24 teev.
Cov kev sib raug zoo tau pom tseeb ntawm kev nce qhov ntau ntxiv ntawm cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® Penfnill ® thiab nws qhov dav dav thiab ntau qhov kev tiv thaiv hypoglycemic. Kev sib xyaw ua ke ntawm cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® Penfill ® tau tiav tom qab 2-3 hnub ntawm kev siv tshuaj.
Tsis muaj qhov sib txawv hauv cov chaw muag tshuaj ntawm Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® Penfill ® hauv cov neeg laus thiab cov laus thiab cov neeg mob me.
Cov chaw kuaj mob tau zoo thiab Kev Nyab Xeeb
Tsib thoob ntiaj teb kev tswj qhib qhov chaw soj ntsuam tau tshawb pom los ntawm cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® hauv kev kho mob rau lub hom phiaj hom rau 26 lossis 52 tus pedals muaj 1360 cov neeg mob ntshav qab zib mellitus (362 cov neeg mob ntshav qab zib mellitus) Yam 1 thiab 998 cov neeg mob ntshav qab zib hom 2). Ob qhov kev tshawb nrhiav pom tau ua rau kev tswj hwm nkaus xwb ntawm Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® kev sib xyaw nrog qhov ncauj tshuaj ntshav qab zib (PHGP) thiab ib koob tshuaj insulin glargine nrog PHGP hauv cov neeg mob ntshav qab zib hom 2 mellitus. Kev tswj hwm ntawm Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® ob zaug ib hnub nyob rau hauv kev sib xyaw nrog PHGP tau piv nrog kev tswj hwm ntawm ob-theem insulin aspart 30 ob zaug hauv ib hnub nrog PHGP hauv ob txoj kev tshawb nrhiav hauv cov neeg mob ntshav qab zib hom 2 Cov. Kev tswj tshuaj ntawm cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® ib zaug ib hnub nyob rau hauv kev sib xyaw nrog insulin aspart kuj tseem piv nrog kev tswj hwm ntawm insulin detemir ib lossis ob zaug hauv ib hnub hauv kev sib xyaw nrog insulin aspartate hauv cov neeg mob ntshav qab zib hom 1 Cov.
Qhov tsis muaj qhov zoo tshaj ntawm kev sib piv cov khoom tau ua pov thawj kom poob nrog Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *)) hauv kev cuam tshuam rau qhov txo qis hauv HbA1c hauv txhua qhov kev tshawb nrhiav hauv kev kho mob ntawm cov neeg mob mus rau lub hom phiaj.
Hauv cov neeg mob uas muaj ntshav qab zib hom 2 uas tsis tau txais kev kho mob insulin thiab cov neeg mob uas tau txais kev kho mob insulin yav dhau los, Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® nrog PHGP muab glycemic zoo sib xws piv rau insulin. Glargin. Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® muab cov kev qhia zoo zoo ntawm cov kab mob glycemic tswj piv rau insulin glargine nrog tsawg zaus ntawm nocturnal hypoglycemia (txhais tau raws li kev mob tshwm sim ntawm hypoglycemia uas tau tshwm sim nruab nrab ntawm 0 teev thiab 6 teev, paub tseeb los ntawm cov txiaj ntsig ntsuas ntsuas ntshav ntshav ntshav qis dua 3.1 mmol / l lossis cov pov thawj uas tus neeg mob xav tau kev pab ntawm peb tog).
Kev tswj cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® ob zaug ib hnub twg muab cov tshuaj zoo sib xws glycemic (HbA)1c) piv nrog biphasic insulin aspart 30, uas tseem tau noj ob zaug ib hnub. Cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® muab qhov zoo tshaj plaws zoo rau hauv kev txo qis cov ntsiab lus ntawm cov piam thaj hauv plasma sai. Thaum siv cov tshuaj Insulin degludec + Insulin aspart * (Cov tshuaj Insulin degludec + Insulin aspart *) ®, lub hom phiaj ntshav plasma qhov tseem ceeb ntawm 5 mmol / L tau tiav nrawm dua rau cov neeg mob piv nrog cov neeg mob kho biphasic insulin aspart 30. Cov tshuaj Insulin degludec + Insulin aspart * (Qhov Insulin degludec + Insulin aspart *) ® Cov kab mob ntshav tsis txaus ua kom npau taws (suav nrog thaum tsaus ntuj). Hauv cov neeg mob uas muaj ntshav qab zib hom 1, kev kho mob nrog Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) a ib hnub ib zaug ua ke nrog insulin aspart ua ntej lwm cov zaub mov noj tau zoo sib xws glycemic tswj (HbA1c thiab yoo plasma ntshav qab zib) nrog ntau dua ntawm cov kab mob ntshav nruab nrab tsawg dua piv nrog lub hauv paus bolus regimen ntawm insulin dstemir thiab insulin aspart nrog txhua pluas noj.
Raws li kev paub txog kev soj xyuas ob ntawm 26-lub lim tiam qhib kev sim npaj raws li "kho rau lub hom phiaj" txoj ntsiab cai cuam tshuam nrog cov neeg mob ntshav qab zib hom 2, cov tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) administ, tswj hwm ob zaug ib hnub, pom tias qis dua qhov tshwm sim ntawm kev paub tseeb tias mob ntshav qab zib tsawg feem ntau thiab cov kev mob tsis txaus siab no piv rau hypoglycemia piv nrog biphasic insulin aspart 30. Cov txiaj ntsig pom tau tias Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® poob qis nws muaj cov roj ntsha yoo ntshav nrawm nrog kev txo qis ntawm cov ntshav qog ntshav qab zib ob leeg thaum kawm thiab thaum tswj kev noj tshuaj los ntawm 16 lub lis piam (Cov lus 1)
Cov lus 1. Cov txiaj ntsig ntawm kev ntsuas kev sojntsuam ntawm cov ntaub ntawv ntawm cov xwm txheej uas pom tseeb tias lub qog ntshav qab zib thaum siv ob zaug ib hnub thaum kawm thiab thaum tswj kev noj tshuaj ntawm 16 lub lis piam
| Kev tsom xam | Tsim lub sij hawm txheeb ze 95% CI | Tsim lub sij hawm txheeb ze 95% CI koob tshuaj txij nkawm lub sijhawm |
| Tag nrho cov naj npawb ntawm paub tseeb tias hypoglycemia tshuaj Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® (2 zaug hauv ib hnub) / biphasic insulin aspart 30 (2 zaug hauv ib hnub) | 0.81 0.67: 0.9S | 0.43 0.31:0.59 |
| Pom zoo tias thaum tsaus ntuj hypoglycemia Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® (2 zaug hauv ib hnub) / insulin biphasic aspart 30 (2 zaug hauv ib hnub) | 0.69 0.55:0.87 | 0.38 0.25,0.58 |
Tsis muaj qhov tseem ceeb ntawm cov tshuaj tiv thaiv kab mob rau insulin tom qab kho nrog Insulin degludec + Insulin aspart * (Insulin degludec + Insulin aspart *) ® rau ncua sijhawm.
Cov yam ntxwv ntawm cov tshuaj Insulin degludec + Insulin aspart
Cov tshuaj sib xyaw ua ke ntawm kev sib txuas ntawm cov tshuaj lom neeg ntawm tib neeg insulin ntawm kev ua lub sijhawm ntev (insulin degludec) thiab kev ua yeeb yaj kiab sai ntawm tib neeg cov tshuaj insulin (insulin aspart) tsim los ntawm kev tso tawm DNA biotechnology siv hom tshuaj Saccharomyces cerevisiae.
Kev sib xyaw ntawm tib neeg cov tshuaj insulin muaj 70% ua kom ntev ntev insulin (insulin degludec) thiab 30% insulin ua haujlwm sai (insulin aspart).
Degludec insulin txawv ntawm tib neeg cov tshuaj insulin thaum tsis muaj threonine amino acid ntawm txoj haujlwm B30 thiab muaj lub ntsej muag sab ua ke muaj cov kua qaub glutamic acid thiab C16 fatty acid, tsim los ntawm recombinant DNA thev naus laus zis siv hom Saccharomyces cerevisiae. Degludec insulin muaj lub cev hnyav ntawm 6103.97.
Insulin aspart yog homologous rau tib neeg cov kua dej, tsuas yog kev hloov pauv ntawm cov proline amino acid ntawm txoj hauj lwm B28 nrog aspartic acid, tsim los ntawm kev siv DNA thev naus laus zis siv kev siv tshuaj Saccharomyces cerevisiae, molecular phaus 5825.8.
Cov tshuaj Insulin Aspart, Bifazik thiab Degludek: tus nqi thiab cov lus qhia
Mob ntshav qab zib mellitus yog ib yam kab mob uas yuav tsum tau kho tas lub neej. Yog li, hauv thawj hom mob thiab hauv kev kis mob siab nrog rau hom thib ob ntawm pathology, cov neeg mob xav tau cov tshuaj insulin tas li, uas pab ua kom cov piam thaj hauv lub cev sai sai, hloov nws mus rau lub zog.
Feem ntau muaj ntshav qab zib, insulin Aspart yog siv. Qhov no yog tshuaj tshuaj ultrashort.
Cov cuab yeej yog qhov sib piv ntawm tib neeg cov tshuaj insulin, uas tau los ntawm kev siv DNA thev naus laus zis siv kev lim ntawm Saccharomyces cerevisiae, qhov twg qhov tshaj tawm ntawm txoj hauj lwm B28 (amino acid) hloov nrog aspartic acid. Tus phaus lwg me me yog 5825.8.
Kev Sau, tso tawm daim ntawv thiab cov nyhuv pharmacological
Biphasic insulin sib xyaw ua ke nrog ua rau Aspart thiab crystalline insulin protamine hauv ib qho ntawm 30 txog 70%.
Qhov no yog rho tawm rau sc administration, muaj xim dawb. 1 milliliter muaj 100 units, thiab ib qho ED sib raug rau 35 mcg ntawm anhydrous insulin Aspart.
Tib neeg cov tshuaj insulin tsim cov txheej txheem insulin receptor complex nrog ib qho receptor nyob sab nraud cytoplasmic cell membrane. Cov tom kawg ua rau lub zog ntawm glycogen synthetase, pyruvate kinase thiab cov enzymes hexokinase.
Qhov kev txo qis hauv qab zib tshwm sim nrog kev nce hauv kev thauj khoom ntawm lub cev thiab kev txhim kho cov nqaij ntawm cov piam thaj. Kev mob ntshav qab zib yog tseem ua tiav los ntawm kev txo qis sijhawm rau kev tso tawm cov piam thaj los ntawm lub siab, glycogenogenesis thiab kev ua haujlwm ntawm lipogenesis.
Biphasic insulin aspart yog tau los ntawm kev siv biotechnological thaum cov kua ntawm cov tshuaj hormones proline hloov los ntawm aspartic acid. Xws li insipins biphasic muaj cov txiaj ntsig zoo rau glycosylated hemoglobin, zoo li tib neeg cov insulin.
Ob qho tshuaj yeeb yog qhov sib luag ntawm cov hniav sib npaug. Txawm li cas los xij, Aspart insulin ua haujlwm nrawm dua li soluble tib neeg txoj kev loj hlob. Lub siab crystalline aspart ntawm cov tshuaj tiv thaiv muaj qhov cuam tshuam ntawm lub sijhawm nruab nrab.
Qhov kev ua tom qab sc tswj hwm ntawm tus neeg sawv cev yog tiav tom qab 15 feeb. Qhov siab tshaj plaws ntawm cov tshuaj tshwm sim 1-4 teev tom qab txhaj tshuaj. Lub sijhawm tiv thaiv ntawm cov nyhuv yog li 24 teev.
Hauv ntshav dej, Cmax ntawm insulin yog 50% ntau dua thaum siv biphasic tib neeg cov insulin. Ntxiv mus, lub sijhawm nruab nrab kom ncav Cmax tsawg dua ib nrab.
T1 / 2 - txog 9 teev, nws qhia txog qhov feem ntawm kev nqus ntawm cov protamin-fraction feem. Lub hauv paus qib tshuaj insulin pom muaj li 15-18 teev tom qab kev tswj hwm.
Tab sis nrog ntshav qab zib hom 2, qhov ua tiav ntawm Cmax yog li 95 feeb. Nws ua kom txog qib qis dua 14 thiab siab dua 0 tom qab kev tswj hwm sc. Seb thaj tsam ntawm kev tswj hwm cuam tshuam rau lub xaib ntawm qhov nqus tsis tau kawm.
Kws Tshuaj
Mechanism ntawm kev ua. Cov tshuaj insulin degludec thiab cov tshuaj insulin aspart tshwj xeeb tshaj tawm rau cov receptor ntawm tib neeg endogenous insulin thiab, cuam tshuam nrog nws, paub lawv cov nyhuv pharmacological zoo ib yam li cov nyhuv ntawm tib neeg insulin. Qhov ua rau lub ntsej muag ntshav ntawm insulin yog vim muaj kev siv cov kua nplaum ntau ntxiv los ntawm cov ntaub so ntswg tom qab kev khi ntawm cov insulin rau cov leeg nqaij thiab cov roj ntsha ua kom lub cev thiab ib qho kev txo qis hauv cov ntshav qabzib ntau los ntawm lub siab.
Cov chaw muag tshuaj muaj txiaj ntsig ntawm cov tshuaj sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart yog qhov sib txawv, thiab qhov kev txiav txim siab ntawm cov tshuaj cuam tshuam cov profiles ntawm qhov kev txiav txim ntawm cov kev ua haujlwm ntawm tus kheej: kev kub ceev insulin aspart thiab insulin degludec ntawm lub sijhawm ntev.
Lub hauv paus ua ke ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart, uas muaj qhov kev ua si ntev (insulin degludec), tom qab sc txhaj tshuaj, ua rau cov kuab tshuaj lom neeg nyob rau hauv cov subcutaneous depot, los ntawm qhov muaj ib qho txuas qeeb qeeb ntawm insulin degludec rau hauv cov ncig, muab cov ntaub ntawv tiaj tus ntawm kev txiav txim siab thiab ruaj khov hypoglycemic effect. Cov nyhuv no tau muab khaws cia ua ke nrog insulin aspart thiab tsis cuam tshuam rau tus nqi ntawm kev nqus ntawm monomers ntawm kev ua yeeb yam sai li sai tau insulin aspart.
Kev sib xyaw ua ke ntawm insulin degludec + insulin aspart pib ua haujlwm sai sai, muab qhov kev xav tau rau insulin tsis ntev tom qab txhaj tshuaj, thaum lub hauv paus tivthaiv muaj qhov sib tiaj, ruaj khov thiab tiv thaiv qhov ntev ntawm kev ua haujlwm uas muab qhov xav tau ntawm insulin. Lub sijhawm ua ntawm ib qho hno ib qho ntawm kev sib xyaw ntawm insulin degludec + insulin aspart yog ntau tshaj 24 teev.
Txoj kab sib txuas ntawm qhov nce ntxiv ntawm qhov koob tshuaj ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart thiab nws qhov dav dav thiab qhov siab tshaj plaws ntawm hypoglycemic effect, Css tau tiav tom qab 2-3 hnub ntawm kev tswj hwm.
Tsis muaj qhov sib txawv hauv cov chaw muag tshuaj ntawm kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart hauv cov neeg laus thiab cov neeg mob me.
Cov chaw kuaj mob tau zoo thiab Kev Nyab Xeeb
Tsib qhov kev xaiv thoob ntiaj teb qhib kev soj ntsuam kev sim ntawm insulin degludec + insulin aspart hauv "kev kho mob rau hom phiaj" tau ua rau 26 lossis 52 lub lis piam nrog 1360 cov neeg mob ntshav qab zib (362 cov neeg mob ntshav qab zib hom 1 thiab 998 cov neeg mob ntshav qab zib hom 2 ) Ob txoj kev tshawb nrhiav tau ua los ntawm ib qho kev tswj hwm ib qho ntawm kev sib xyaw ntawm insulin degludec + insulin aspart hauv kev sib xyaw nrog lub qhov ncauj hypoglycemic (PHGP) thiab kev tswj hwm ib leeg ntawm insulin glargine nrog PHGP hauv cov neeg mob uas muaj ntshav qab zib hom 2. Los ntawm kev tswj hwm ntawm insulin degludec + insulin aspart 2 zaug hauv ib hnub yog koom ua ke nrog PHGP tau sib piv nrog kev tswj hwm ntawm biphasic insulin aspart 30 ob zaug txhua hnub hauv kev sib xyaw ua ke nrog PHGP hauv ob txoj kev tshawb nrhiav hauv cov neeg mob uas muaj ntshav qab zib hom 2. insulin aspart ib hnub ib zaug nyob rau hauv kev sib xyaw nrog insulin aspart kuj tseem piv nrog kev tswj hwm ntawm insulin detemir 1 lossis 2 zaug hauv ib hnub nyob rau hauv kev sib xyaw nrog insulin aspart hauv cov neeg mob uas muaj hom 1 ntshav qab zib mellitus.
Tsis muaj qhov zoo tshaj ntawm kev sib piv cov tshuaj dua li kev sib xyaw ntawm insulin degludec + insulin aspart in relation to qhov txo qis hauv HbA1c hauv txhua qhov kev tshawb nrhiav hauv kev kho mob ntawm cov neeg mob mus rau lub hom phiaj.
Hauv cov neeg mob uas muaj ntshav qab zib hom 2 uas tsis tau txais kev kho mob insulin thiab cov neeg mob uas tau txais kev kho mob insulin yav dhau los, kev sib xyaw ntawm insulin degludec + insulin aspart nrog PHGP muab kev tswj zoo glycemic piv rau insulin glargine. Kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart muab kev tswj hwm zoo sib xyaw ua ke sib piv nrog insulin glargine nrog tsawg zaus ntawm nocturnal hypoglycemia (txhais raws li kev mob tshwm sim ntawm hypoglycemia uas tau tshwm sim nruab nrab ntawm 0 txog 6 teev sawv ntxov, paub tseeb los ntawm kev ntsuas ntshav ntshav muaj zog tsawg dua 3.1 mmol / l lossis xav tau kev pab rau neeg mob los ntawm peb tog).
Cov lus qhia ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart 2 zaug hauv ib hnub ib zaug muab cov kev tswj zoo sib xws glycemic (HbA1c) piv nrog biphasic insulin aspart 30, uas tseem tau noj 2 zaug nyob rau ib hnub. Kev sib xyaw ua ke ntawm insulin degludec + insulin aspart muab qhov ua tau zoo tshaj plaws hauv kev txo qis ntshav qab zib ntau ntau. Thaum siv kev sib xyaw ua ke ntawm insulin degludec + insulin aspart, phiaj plasma ntshav qab zib qhov tseem ceeb ntawm 5 mmol / L tau tiav sai hauv cov neeg mob piv nrog cov neeg mob kho nrog biphasic insulin aspart 30. Kev sib xyaw ua ke ntawm insulin degludec + insulin aspart tsawg feem ntau ua rau mob ntshav qab zib (nrog rau thaum tsaus ntuj) Cov. Hauv cov neeg mob uas muaj hom 1 mob ntshav qab zib mellitus, kev kho mob nrog kev sib xyaw ntawm insulin degludec + insulin aspart 1 zaug hauv ib hnub nyob rau hauv kev sib xyaw nrog insulin aspart qhia zoo sib xws glycemic tswj ua ntej lwm yam noj mov (HbA1c thiab yoo plasma ntshav qab zib) nrog ntau dua ntawm cov kab mob ntshav nruab nrab tsawg dua piv nrog lub hauv paus bolus regimen ntawm insulin detemir thiab insulin aspart nrog txhua pluas noj.
Raws li kev soj xyuas meta-kev tshawb nrhiav ntawm ob lub sijhawm 26-lub limtiam qhib kev sim tau tsim raws li "kho rau lub hom phiaj" cov ntsiab lus koom nrog cov neeg mob ntshav qab zib hom 2, kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart, siv 2 zaug hauv ib hnub, pom tias tsawg dua qhov tshwm sim ntawm cov mob uas tau lees paub hypoglycemia feem ntau thiab ntu kev txheeb xyuas qhov mob nocturnal hypoglycemia piv nrog insulin biphasic aspart 30. Ib qho kev soj xyuas meta tau qhia tias kev sib xyaw ntawm insulin degludec + insulin aspart txo qis ntshav qabzib concentration. yoo ntshav nrog txo qis kev pheej hmoo ntawm lub qog ntshav qab zib ob leeg thaum kawm thiab thaum tswj kev noj tshuaj los ntawm 16 lub lis piam. Cov teeb meem txheeb ze tsim nyog (95% CI) ntawm tag nrho cov naj npawb ntawm kev lees paub txog kev mob ntshav qab zib kev sib xyaw ua ke ntawm insulin degludec + insulin aspart (2 zaug hauv ib hnub) / insulin biphasic aspart 30 (2 zaug hauv ib hnub) thaum lub sijhawm kawm yog 0.81 (0.67, 0.98 ), thaum lub sij hawm txij nkawm ntawm koob tshuaj - 0.69 (0.55, 0.87), tus txheeb ze zaus ntawm paub tseeb tias hmo ntuj hypoglycemia - 0.43 (0.31, 0.59) thaum lub sijhawm kawm thiab 0.38 (0.25, 0.58) lub sij hawm kho koob.
Tsis muaj qhov tseem ceeb ntawm cov tshuaj tiv thaiv kab mob rau cov tshuaj insulin tom qab kho mob nrog kev sib xyaw ntawm insulin degludec + insulin aspart rau ncua sijhawm.
Kev Tsis Txaus Siab Tom qab txhaj tshuaj sc, qhov tsim ntawm soluble ruaj khov degludec insulin multihexamers tshwm sim, uas tsim cov insulin rau hauv subcutaneous adipose nqaij thiab tsis cuam tshuam nrog kev tso tawm sai ntawm insulin aspart monomers mus rau hauv cov hlab ntshav. Multihexamers maj mam sib cais, tso tawm degludec insulin monomers, vim tias nws maj mam nkag mus rau hauv cov hlab ntshav. Css ib qho kev txuam ntawm superlong kev ua (insulin degludec) hauv cov ntshav ntshav tau tiav 2-3 hnub tom qab kev qhia txog kev sib xyaw ua ke ntawm insulin degludec + insulin aspart.
Cov kev ntsuas pom zoo ntawm kev nqus sai ntawm cov tshuaj insulin aspart yog khaws cia hauv kev sib xyaw ntawm insulin degludec + insulin aspart. Tus kws kho mob cov ntaub ntawv ntawm cov tshuaj insulin aspart tshwm 14 feeb tom qab txhaj, Cmax saib tom qab 72 feeb
Kev Tsis Txaus Siab Qhov tsom - lub sijhawm tiv thaiv profile tom qab ib qho sc sc sib txawv ntawm 0.4, 0.6, thiab 0.8 U / kg ua ke ntawm insulin degludec + insulin aspart hauv cov neeg mob uas muaj hom 1 mob ntshav qab zib mellitus thiab hom 2 mob ntshav qab zib mellitus qhia kev nce ntxiv nrog rau kev nce ntxiv rau ob qho tag nrho ntawm kev sib xyaw.
Tshuaj insulin aspart pom tias muaj koob tshuaj ntau rau hauv Cmax thiab ib nyuag ntau dua qhov koob tshuaj-koob ntau dua ntawm AUC0–12 tom qab ib qho sc coj ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart hauv cov neeg mob uas muaj hom 1 ntshav qab zib mellitus thiab hom 2 mob ntshav qab zib mellitus.
Qhov tshuaj insulin degludec pom tias muaj koob tshuaj ntau txaus hauv Cmax thiab AUC0–120 nrog ib qho sc thawj coj ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart hauv cov neeg mob uas muaj hom 1 ntshav qab zib mellitus thiab hom 2 mob ntshav qab zib mellitus.
Qhov pib ntawm cov nyhuv rau kev sib xyaw ua ke - insulin aspart - thaj tsam 14 feeb tom qab txhaj tshuaj, Cmax - 72 feeb Ntshav Css kev sib xyaw ua ke - insulin degludec - tau tiav los ntawm 3-4 hnub tom qab kev tswj hwm ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart.
Kev xa Khoom. Qhov sib koom ua ke ntawm degludec insulin rau cov ntshiab albumin sib raug rau lub peev xwm khi ntawm plasma protein (> 99%) hauv tib neeg cov ntshav ntshav. Hauv cov tshuaj insulin aspart, lub plasma protein khi qhov khi muaj peev xwm qis dua (T1/2 kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart tom qab sc txhaj tshuaj yog txiav txim siab los ntawm tus nqi ntawm kev nqus ntawm subcutaneous ntaub so ntswg. T1/2 Degludec insulin yog kwv yees li 25 teev thiab raug muab tshuaj ywj siab.
Kab Zuag. Tag nrho cov txiaj ntsig ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart yog siv rau kev noj tshuaj ntawm lub hauv paus pob (insulin degludec) thiab qhov sib xyaw ua ke (insulin aspart) hauv hom 1 thiab hom 2 mob ntshav qab zib mellitus.
Cov pab pawg neeg tshwj xeeb
Tsis muaj qhov sib txawv hauv cov khoom lag luam pharmacokinetic ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart nyob ntawm tus tub los ntxhais ntawm cov neeg mob.
Cov neeg laus, cov neeg mob ntawm cov pab pawg sib txawv, cov neeg mob uas lub raum tsis ua haujlwm lossis mob rau daim siab. Tsis muaj qhov sib txawv hauv kev kho mob hauv cov chaw muag tshuaj ntawm kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart ntawm cov neeg laus thiab cov neeg mob hluas, ntawm cov neeg mob ntawm cov pab pawg sib txawv, ntawm cov neeg mob uas tsis muaj mob raum thiab mob siab thiab cov neeg mob noj qab haus huv.
Geriatrics Cov chaw muag tshuaj thiab pharmacodynamic muaj txiaj ntsig ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart tau kawm hauv 13 cov neeg hluas (18-35 xyoo) thiab 15 tus neeg laus (≥65 xyoo) nrog hom 1 ntshav qab zib mellitus tom qab 2 zaug kev txhaj tshuaj ntawm 0.5 U / kg: ib qho yog kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart thiab ib qho yog ob-theem insulin aspart. Tag nrho cov kev siv ntawm cov tshuaj insulin aspart sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart (raws li AUC0–12 insulin aspart) hauv cov neeg mob cov laus feem ntau nyiam piv rau cov neeg hluas. Tag nrho cov kev siv ntawm cov tshuaj insulin degludec ua ke ntawm cov tshuaj insulin degludec + insulin aspart (raws li AUC0–120 insulin degludec) thiab cov chaw muab tshuaj rau hauv kev sib xyaw ua ke ntawm insulin degludec + insulin aspart (raws li AUC0–24 insulin degludec) zoo ib yam li cov neeg hluas thiab cov laus neeg mob ntshav qab zib hom 1, txawm hais tias cov sib txawv hauv cov neeg laus sib txawv hauv cov neeg laus laus dua.
Menyuam yaus thiab tub ntxhais hluas. Cov chaw muag tshuaj ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart hauv kev tshawb fawb hauv cov menyuam yaus (6 years11 xyoo) thiab cov hluas (12-18 xyoo) nrog hom 1 ntshav qab zib mellitus piv rau cov neeg mob hauv cov neeg laus uas tau txhaj ib zaug.
Tag nrho cov kev xav thiab Cmax cov tshuaj insulin yog qhov ntau dua hauv cov menyuam yaus dua li cov laus, thiab tib yam rau cov hluas thiab cov laus.
Cov tshuaj pharmacokinetic ntawm degludec insulin hauv cov menyuam yaus thiab cov hluas muaj ntshav qab zib hom 1 piv rau cov neeg mob hauv cov neeg laus. Tawm tsam keeb kwm ntawm kev txhaj tshuaj ib zaug ntawm koob tshuaj degludec insulin hauv cov neeg mob uas muaj hom 1 ntshav qab zib mellitus, nws tau pom tias tag nrho cov txiaj ntsig ntawm cov tshuaj rau hauv cov menyuam yaus thiab cov tub ntxhais hluas yog siab dua qhov ntawd hauv cov neeg laus.
Paul Cov nyhuv ntawm kev sib deev ntawm cov pharmacokinetics ntawm cov tib neeg sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart tau raug soj ntsuam hauv kev tshuaj ntsuam ntawm ntau yam pharmacokinetic thiab pharmacodynamic cov kev tshawb fawb. Feem ntau, tsis muaj qhov sib txawv loj hauv qhov chaw ua hauj lwm pharmacokinetic ntawm insulin degludec lossis insulin aspart ntawm cov poj niam thiab txiv neej.
Kev pham Cov nyhuv ntawm lub cev lub cev qhov ntsuas (BMI) ntawm pharmacokinetics ntawm cov tib neeg sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart tau kawm hauv kev soj ntsuam ntawm kev tshawb fawb hla-pharmacokinetic thiab pharmacodynamic. Hauv cov neeg mob uas muaj hom 1 mob ntshav qab zib mellitus, tsis muaj kev sib raug zoo tau pom ntawm kis ntawm insulin degulinec thiab BMI. Hauv cov neeg mob uas muaj ntshav qab zib hom 1 thiab ntshav qab zib hom 2, txoj kev nyiam ua kom lub ntsej muag qis dua qis ntawm kev pom zoo ntawm degludec insulin nrog kev nce hauv BMI tau tshwm sim. Rau insulin aspart, tsis muaj kev sib txuas ntawm BMI thiab kev sib kis hauv cov neeg mob uas muaj ntshav qab zib hom 1 lossis hom 2.
Haiv neeg thiab pawg. Cov nyhuv ntawm haiv neeg thiab haiv neeg ntawm cov chaw muag tshuaj ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart tsis tau kawm. Cov hauv paus ntawm kev sib xyaw ua ke - insulin degludec - tau kawm hauv pharmacokinetic thiab pharmacodynamic kev tshawb fawb hauv Asmeskas Neeg Asmeskas ntawm haiv neeg Mev lossis neeg Latin (n = 18), cov neeg tawv nqaij dawb ntawm haiv neeg Hispanic lossis Hispanic keeb kwm (n = 22), thiab cov neeg tawv nqaij dawb ntawm haiv neeg Hispanic lossis Latino keeb kwm (n = 23) nrog Hom 2 mob ntshav qab zib mellitus Tsis muaj qhov sib txawv li cas ntawm cov haiv neeg thiab pawg neeg tau tshawb fawb.
Cev xeeb tub Cov txiaj ntsig ntawm kev xeeb tub ntawm daim ntawv tso cai thiab cov khw muag tshuaj ntawm kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart tsis tau kawm (saib. "Siv hauv cev xeeb tub thiab lactation").
Tsis hlauv. Cov nyhuv ntawm lub raum tsis ua hauj lwm rau lub pharmacokinetics ntawm kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart tsis tau kawm. Cov hauv paus ntawm kev sib xyaw ua ke - insulin degludec (nrog rau kev qhia ntawm ib qho sc koob tshuaj 0.4 U / kg) - tau kawm hauv pharmacokinetic cov kev tshawb fawb hauv 32 tus neeg (n = 4-8 / pab pawg) nrog kev ua haujlwm tsis zoo los yog mob raum ua haujlwm / mob raum tsis ua haujlwm. Cov. Lub raum tsis ua haujlwm raug txiav txim siab ua raws Cl Clininine: ≥90 ml / min (ib txwm), 60–89 ml / min (me me), 30–59 ml / min (mob hnyav) thiab s / c koob tshuaj 0.08 U / kg insulin aspart (kev ua haujlwm sai ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart) raug soj ntsuam hauv kev tshawb fawb hauv cov neeg muaj lub raum rov qab ua haujlwm, me, mob hnyav lossis mob hnyav (tab sis tsis tas yuav muaj cov mob hemodialysis) lub raum tsis ua haujlwm. Hauv qhov kev tshawb fawb no, tsis muaj pom meej meej ntawm kev tsim cov tshuaj tawm ntawm AUC thiab Cmax insulin aspart.
Daim siab ua haujlwm. Cov nyhuv ntawm daim siab ua rau lub pharmacokinetics ntawm kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart tsis tau kawm. Qhov tseem ceeb ntawm kev sib xyaw ua ke - insulin degludec - tau kawm hauv pharmacokinetic txoj kev tshawb fawb hauv 24 tus neeg (n = 6 / pab pawg) nrog lub siab lossis lub siab ua haujlwm tsis zoo (mob me, nruab nrab thiab mob hnyav hepatic tsis txaus) tom qab kev siv ib koob s / c koob tshuaj (0.4 PIECES / kg) cov tshuaj insulin degludec. Tsis muaj qhov sib txawv hauv cov chaw muag tshuaj ntawm insulin degludec tau tshawb pom ntawm cov neeg noj qab haus huv thiab cov neeg muaj lub siab tsis zoo (saib "Kev Ceeb Toom").
Hauv kev kawm qhib kev txhaj tshuaj ib zaug ntawm 0.06 U / kg ntawm insulin aspart (kev tiv thaiv sai ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart) tau muab sc rau 24 tus neeg mob (n = 6 / pab pawg) nrog kev sib txawv ntawm daim siab tsis ua hauj lwm (mob me, nruab nrab, mob hnyav). Hauv qhov kev tshawb fawb no, tsis muaj kev sib txheeb pom ntawm qib siab ntawm daim siab ua haujlwm thiab lub pharmacokinetics ntawm insulin aspart.
Kev Kawm Kev Nyab Xeeb Preclinical
Cov ntaub ntawv tshaj tawm raws li kev tshawb fawb txog kev nyab xeeb ntawm pharmacological, kev ua kom lub cev muaj tshuaj ntau ntau, muaj peev xwm ua rau lub cev, cov tshuaj lom neeg rau lub cev tsis ua haujlwm, tsis tau qhia txog kev puas tsuaj rau tib neeg. Qhov piv ntawm cov khoom noj ntawm metabolic thiab mitogenic ntawm degludec insulin yog qhov zoo sib xws ntawm tib neeg cov insulin.
Cev xeeb tub thiab lactation
Kev siv ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart thaum cev xeeb tub yog contraindicated, vim hais tias tsis muaj kev paub dhau los nrog kev siv nws thaum cev xeeb tub. Cov kev tshawb fawb ntawm kev ua me nyuam tsiaj muaj nuj nqi tsis tau qhia qhov sib txawv ntawm degludec insulin thiab insulin tib neeg qhov tseeb hais txog embryotoxicity thiab teratogenicity.
Kev siv ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart thaum pub mis niam yog contraindicated, vim hais tias Tsis muaj kev sim kho mob nrog cov pojniam kev tub rog.
Cov kev tshawb fawb tsiaj tau qhia tias hauv cov nas, degludec insulin yog txia hauv cov kua mis, nws cov ntsiab lus hauv cov kua mis muaj qis dua hauv ntshav ntshav. Kuj tsis paub meej tias insulin degludec ua rau niam cov kua mis tawm ntawm tus poj niam.
Cuam Tshuam. Cov kev tshawb fawb tsiaj tsis pom muaj qhov tsis zoo ntawm degludec insulin ntawm kev ua me nyuam yaus.
FDA Fetal Action Qeb - C.
Kev tshawb nrhiav qhov tsim nyog thiab nruj tswj hwm ntawm kev siv ntawm kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart hauv cov poj niam cev xeeb tub tsis tau ua. Thaum npaj kev cev xeeb tub lossis tsim nws, cov neeg mob yuav tsum sib tham txog kev siv tshuaj nrog lawv tus kws kho mob. Vim tias cov kev tshawb fawb txog tsiaj yug menyuam tsis tas yuav paub txog cov teebmeem hauv tib neeg, kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart yuav tsum tau siv thaum cev xeeb tub tsuas yog tias qhov xav tau ntawm kev kho mob tshaj qhov ua rau muaj qhov pheej hmoo rau tus me nyuam hauv plab. Rau cov neeg mob uas muaj keeb kwm mob ntshav qab zib los yog mob ntshav qab zib hauv lub cev, tswj kev tswj cov zaub mov zoo ua ntej kev xeeb tub thiab thaum cev xeeb tub yog qhov tseem ceeb. Qhov kev xav tau rau cov tshuaj insulin tuaj yeem txo qis thaum thawj peb lub hlis thaum cev xeeb tub, raws li txoj cai, nws nce ntxiv thaum lub caij thib ob thiab thib peb thiab txiav tawm sai tom qab yug menyuam. Kev ua tib zoo saib xyuas cov ntshav qabzib yog ib qho tseem ceeb hauv cov neeg mob no.
Nws tsis paub meej tias puas yog ntxig degludec / aspart insulin yog tawm hauv niam mis. Txij li ntau yam tshuaj yeeb dej caw, suav nrog tib neeg cov tshuaj insulin, raug tawm hauv niam cov kua mis, kev ceeb toom yuav tsum tau siv thaum siv cov tshuaj insulin degludec + insulin aspart hauv cov niam tsev laus. Cov poj niam muaj ntshav qab zib lub sij hawm lactation yuav tau hloov pauv tshuaj insulin, phiaj xwm pub mis, lossis ob qho tib si.
Kev phiv tshuaj ntawm cov tshuaj Insulin degludec + Insulin aspart
Cov kev mob tshwm sim feem ntau tau tshaj tawm thaum kho mob yog hypoglycemia (saib Qhia txog cov kev phiv rau ib tus neeg).
Txhua qhov kev mob tshwm sim tau piav qhia hauv qab no, raws li cov ntaub ntawv los ntawm kev sim tshuaj, suav tau raws pawg MedDRA thiab khoom nruab nrog cev. Qhov tshwm sim ntawm cov kev mob tshwm sim txhais tau hais tias ntau zaus (/1 / 10), feem ntau (≥1 / 100 rau cov tshuaj, tuaj yeem cuam tshuam tus neeg mob lub neej.
Thaum siv kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart, kev tsis haum lub cev (nrog rau o ntawm daim nplaig lossis daim di ncauj, zawv plab, xeev siab, nkees thiab tawv nqaij) thiab urticaria tsis tshua muaj.
Kev ua xua tsis haum. Thaum siv cov tshuaj insulin, suav nrog kev sib xyaw ua ke ntawm insulin degludec + insulin aspart, lub cev tiv thaiv tsis haum lub cev feem ntau muaj peev xwm tsim tau, suav nrog anaphylaxis, kev tawm tsam ntawm cov tawv nqaij, kev mob khaus khaus, bronchospasm, hypotension thiab poob siab, cov tshuaj tiv thaiv no tuaj yeem ua rau tuag tau (saib "Kev Ceebtoom") Cov.
Hypersensitivity (manifested los ntawm o ntawm daim nplaig thiab daim di ncauj, raws plab, xeev siab, qaug zog thiab khaus) thiab urticaria tau sau tseg ntawm 0.5% cov neeg mob tau txais kev sib txuas ntawm cov tshuaj insulin degludec + insulin aspart.
Kev ntshav siab. Kev mob ntshav qog ntshav siab tuaj yeem tsim kho yog tias qhov koob tshuaj insulin ntau dhau rau hauv kev sib txuas nrog tus neeg mob xav tau. Kev mob ntshav nce siab ntau hauv lub cev tuaj yeem ua rau tsis nco qab thiab / lossis rov huam, ib ntus lossis tsis tuaj yeem ua haujlwm ntawm lub hlwb kom mus txog rau qhov ua rau muaj kev ploj tuag. Cov tsos mob ntawm tus mob hypoglycemia, raws li txoj cai, tshwm sim sai. Cov no suav nrog kev tawm hws txias, pallor ntawm daim tawv nqaij, ua rau qaug zog, tshee lossis tshee tshee, ntxhov siab, nkees txawv lossis qaug zog, tsis meej pem, txo qis qis, nkees, kev tshaib nqhis, tsis pom kev, mob taub hau, xeev siab, lub plawv dhia.
Lipodystrophy. Lipodystrophy (suav nrog lipohypertrophy, lipoatrophy) tuaj yeem txhim kho ntawm qhov chaw txhaj tshuaj. Kev ua raws li cov cai ntawm kev hloov pauv chaw txhaj tshuaj hauv tib thaj chaw ua haujlwm pab txo qis kev pheej hmoo ntawm kev tsim cov tshuaj tiv thaiv no.
Lipodystrophy. Kev siv lub sij hawm ntev ntawm insulin, suav nrog kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart, tuaj yeem ua rau lipodystrophy ntawm qhov chaw uas rov qab tso tshuaj insulin. Lipodystrophy suav nrog lipohypertrophy (ua rau tuab ntawm daim ntaub adipose) thiab lipoatrophy (ua rau cov qog ntawm cov ntaub so ntswg) thiab yuav cuam tshuam rau kev nqus insulin. Koj yuav tsum tau hloov pauv qhov chaw txhaj tshuaj ntawm cov tshuaj insulin hauv tib thaj av ib puag ncig kom txo tau txoj kev pheej hmoo ntawm lipodystrophy. Cov chaw kho mob tau tshaj tawm txog lipodystrophy hauv 0.1% ntawm cov neeg mob, kho nrog kev sib xyaw ua ke ntawm insulin degludec + insulin aspart.
Cov tshuaj tiv thaiv ntawm qhov chaw txhaj tshuaj. Hauv cov neeg mob tau txais kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart, cov tshuaj tiv thaiv tau pom ntawm qhov chaw txhaj tshuaj (hematoma, mob, mob ntshav hauv zos, erythema, sib txuas ntawm cov nqaij ntswg nodules, o, ua kom tawv nqaij, khaus, khaus thiab nruj ntawm qhov chaw txhaj tshuaj). Feem ntau qhov tshwm sim ntawm qhov chaw txhaj tshuaj yog qhov me, ib ntus, thiab feem ntau ploj nrog kev kho txuas ntxiv.
Cov tshuaj tiv thaiv ntawm qhov chaw txhaj tshuaj. Cov neeg mob uas tau txais cov tshuaj insulin degludec + insulin aspart sib xyaw ua ke yuav tsim kev tawm tsam ntawm qhov chaw txhaj tshuaj, suav nrog hematoma, mob, mob ntshav, mob erythema, mob taub hau, o, tawv nqaij, ua rau tawv nqaij, khaus, hnov ntawm qhov sov, thiab nruj ntawm qhov chaw txhaj tshuaj. Hauv qhov chaw txhaj tshuaj, cov tshuaj tiv thaiv ntawm qhov chaw txhaj tshuaj tau pom nyob hauv 2% ntawm cov neeg mob, kho nrog kev sib xyaw ua ke ntawm insulin degludec + insulin aspart.
Qhov hnyav nce. Kev hnyav nce tuaj yeem pom nrog kev kho insulin, suav nrog thaum siv kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart, thiab yog ib qho kev tshaj tawm ntawm anabolic teebmeem ntawm insulin. Hauv qhov chaw kho mob, cov neeg mob ntshav qab zib hom 1 uas tau txais insulin degludec + insulin aspart sib xyaw ua ke muaj qhov hnyav nruab nrab ntawm lub cev hnyav ntawm 2.8 kg, thiab cov neeg mob ntshav qab zib hom 2 uas tau txais insulin degludec + insulin aspart tau txais qhov nruab nrab ntawm 1 , 6 kg.
Sab Sij Huam Phem. Cov tshuaj insulin, suav nrog kev sib xyaw ua ke ntawm insulin degludec + insulin aspart, tuaj yeem ua rau sodium tuav thiab edema. Hauv qhov chaw kho mob, kho mob peripheral edema tau pom nyob rau hauv 2.2% ntawm cov neeg mob ntshav qab zib hom 1 thiab 1.8% ntawm cov neeg mob ntshav qab zib hom 2 uas tau txais kev sib xyaw ntawm insulin degludec + insulin aspart.
Menyuam yaus thiab tub ntxhais hluas. Cov chaw muag tshuaj ntawm cov tshuaj sib xyaw ua ke ntawm insulin degludec + insulin aspart tau kawm hauv cov menyuam yaus thiab cov hluas hauv qab 18 xyoo (saib. Pharmacokinetics). Cov kev kawm txog kev ua tau zoo thiab kev nyab xeeb hauv cov menyuam yaus thiab cov hluas tsis tau ua tiav.
Cov pab pawg neeg tshwj xeeb. Thaum kuaj mob, tsis muaj qhov sib txawv ntawm qhov tshwm sim ntau zaus, hom, lossis mob hnyav ntawm cov neeg mob laus, cov neeg mob uas lub raum tsis ua haujlwm lossis mob siab, thiab cov neeg mob thoob plaws.
Cov kev tshawb fawb tshawb nrhiav Kev paub
Txij li cov kev sim kho mob tau ua nrog cov kev mob sib txawv, qhov tshwm sim ntawm cov kev tsis zoo tshwm sim hauv cov kev tshawb fawb no tsis tuaj yeem piv ncaj qha nrog kev ntsuas hauv lwm qhov kev sim tshuaj thiab kwv yees tias qhov tshwm sim ntawm cov kev mob tshwm sim hauv kev soj ntsuam.
Kev nyab xeeb ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart hauv cov neeg mob uas muaj hom 1 thiab hom 2 ntshav qab zib mellitus tau raug soj ntsuam hauv 5 qhov kev sim ua raws txoj ntsiab cai "kho rau lub hom phiaj", kav ntev txog 6-12 lub hlis.
Kev kawm txog kev nyab xeeb ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart hauv cov neeg mob ntshav qab zib hom 1 mob ntshav qab zib tau suav nrog 362 cov neeg mob, qhov nruab nrab lub sijhawm tau raug yog 43 lub lis piam. Lub hnub nyoog nruab nrab ntawm cov neeg mob yog 41 xyoo, thiab 1% ntawm cov neeg mob hnub nyoog tshaj 75 xyoo. Tsib caug ob feem pua yog txiv neej, 91% yog tawv nqaij dawb, 3% yog neeg Asmeskas-Asmeskas, thiab 3% yog neeg Hispanic. Qhov nruab nrab BMI yog 26 kg / m 2. Qhov nruab nrab ntev ntawm ntshav qab zib yog 17 xyoo, thiab qhov nruab nrab HbA1c thaum pib ntawm kev kawm - 8.3%. Keeb kwm ntawm mob neuropathy, ophthalmopathy, nephropathy, thiab mob plawv thaum pib ntawm kev tshawb fawb tau qhia hauv 19, 25, 6, thiab 4% ntawm tus neeg mob, feem. Qhov txiaj ntsig GFR thaum pib ntawm kev tshawb fawb yog 88 ml / min / 1.73 m 2, thiab 6% ntawm cov neeg mob tau GFR tsawg dua 60 ml / min / 1.73 hli 2.
Lwm qhov kev tshawb fawb txog kev nyab xeeb ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart suav nrog 998 cov neeg mob uas muaj ntshav qab zib hom 2, qhov nruab nrab ntev tau yog 24 lub lis piam. Qhov nruab nrab hnub nyoog ntawm cov neeg mob yog 58 xyoo, thiab 3% yog dhau 75 xyoo. Tsib caug-plaub feem pua yog txiv neej, 44% yog tawv nqaij dawb, 4% Neeg Asmeskas tawv nqaij, thiab 6% yog neeg Hispanic. Qhov nruab nrab BMI yog 29 kg / m 2. Qhov sijhawm nruab nrab ntawm ntshav qab zib yog 12 xyoo, qhov nruab nrab HbA1c thaum pib ntawm kev kawm - 8.5%. Keeb kwm ntawm mob neuropathy, ophthalmopathy, nephropathy, thiab mob plawv thaum pib ntawm kev tshawb fawb tau qhia hauv 15, 21, 10, thiab 1% ntawm tus mob, feem. Thaum pib, lub ntsiab lus GFR yog 84 ml / min / 1.73 m 2 thiab hauv 11% ntawm cov neeg mob qis dua 60 ml / min / 1,73 m 2.
Cov kev phiv tshuaj tiv thaiv kab mob (tshwj tsis yog muaj ntshav tsis txaus) pom thaum lub sijhawm kuaj mob hauv cov neeg mob uas muaj hom 1 thiab hom 2 mob ntshav qab zib mellitus kho nrog kev sib xyaw ntawm insulin degludec + insulin aspart tau muab rau hauv qab no. Cov kev tsis haum siab tau txhais tau tias yog cov kev tiv thaiv tshwm sim hauv ≥5% ntawm cov neeg mob hauv qhov kev kawm. Hypoglycemia tsis qhia thiab raug tham hauv ntu tshwj xeeb hauv qab no.
Kev phiv tshuaj tiv thaiv pom nyob rau hauv ≥5% ntawm cov neeg mob uas muaj mob ntshav qab zib hom 1 hauv kev kho mob nrog insulin degludec + insulin aspart (N = 362)
Mob taubhau 9.7%.
Sab saud ua pa kab mob 9.1%.
Cov kev phiv tshuaj pom nyob rau hauv in5% nrog hom 2 mob ntshav qab zib mellitus hauv kev kho mob nrog insulin degludec + insulin aspart (N = 998)
Cov kab mob ua pa sab saud 5.7%.
Mob taub hau 5.6%.
Kev mob ntshav siab yog qhov feem ntau pom tshwm sim tsis zoo hauv cov neeg mob uas siv cov tshuaj insulin, suav nrog kev sib xyaw ntawm insulin degludec + insulin aspart (saib "Kev ceev faj"). Qhov ntau zaus ntawm kev cim kho hypoglycemia yog nyob ntawm lub ntsiab lus siv rau lub tswvyim ntawm kev mob ntshav qab zib, xws li mob ntshav qab zib, koob tshuaj insulin, kev siv ntshav qabzib ntau, kev kho mob tom qab thiab lwm yam sab hauv thiab sab nraud rau tus neeg mob. Rau cov laj thawj no, kev sib piv cov xwm txheej ntawm hypoglycemia hauv kev sim tshuaj sim ntawm kev sib xyaw ntawm insulin degludec + insulin aspart nrog cov xwm txheej ntawm hypoglycemia nrog lwm tus neeg sawv cev yuav ua rau muaj qhov tsis zoo thiab tej zaum yuav tsis yog tus sawv cev ntawm kev ntsuas hypoglycemia pom hauv kev soj ntsuam.
Hauv qab no yog qhov tshwm sim ntawm kev mob ntshav qab zib hauv kev tshawb nrhiav hauv cov neeg mob uas muaj hom 1 thiab ntshav qab zib hom 2 uas tau txais kev sib xyaw ntawm insulin degludec + insulin aspart. Kev mob ntshav nce siab ntau heev txhais tau tias yog ib qho xwm txheej xav tau kev pab ntawm lwm tus neeg los txhaj cov khoom noj carbohydrates, glucagon, lossis lwm yam kev rov ua haujlwm.
Hauv cov kev tshawb fawb soj ntsuam, kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart hypoglycemia tau txhais tias qhov xwm txheej ntawm cov ntshav qog ntshav ntshav tsawg (1), lossis ib qho xwm txheej uas cov ntshav kuaj ntshav lossis ntshav ntshav qab zib tsawg dua 56 mg / dl lossis tag nrho cov ntshav qabzib tsawg dua 50 mg / dl (i.e. nrog lossis tsis muaj tus mob hypoglycemic) - (2).
Feem pua ntawm cov neeg mob ntshav qab zib hom 1 uas tau ntsib yam tsawg kawg 1 ntu ntawm cov ntshav qog ntshav qab zib (1) lossis hypoglycemia (2) hauv kev soj ntsuam cov neeg laus
Hauv Kev Tshawb Fawb A, cov neeg mob tau txais kev sib xyaw ntawm insulin degludec + insulin aspart (1 zaug hauv ib hnub) ntxiv rau insulin aspart (2 zaug hauv ib hnub) rau 52 lub lis piam (N = 362).
Kev Tshuaj Ntshav Siab (1) 13.3%.
Kev Ntshav Qab Zib (2) 95%.
Feem pua ntawm cov neeg mob ntshav qab zib hom 2 uas tau ntsib yam tsawg kawg 1 ntu ntawm cov ntshav qog ntshav qab zib (1) lossis hypoglycemia (2) hauv kev soj ntsuam cov neeg laus
Hauv kev kawm B, cov neeg mob tau txais kev sib xyaw ntawm insulin degludec + insulin aspart (1 zaug hauv ib hnub), insulin yooj yim thiab yav dhau los 2 lossis ntau dua PHGP (N = 265).
Hauv Kev Tshawb Fawb C, cov neeg mob tau txais kev sib xyaw ua ke ntawm insulin degludec + insulin aspart (1 zaug hauv ib hnub), insulin ua ntej (1 zaug hauv ib hnub), thiab 1 lossis ntau dua PHGP (N = 230).
Hauv kev kawm D, cov neeg mob tau txais kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart (2 zaug hauv ib hnub), yav tas los 1-2 zaug hauv ib hnub, pre / tus kheej sib xyaw, nrog / tsis muaj PHGP (N = 224).
Hauv kev kawm E, cov neeg mob tau txais kev sib xyaw ua ke ntawm insulin degludec + insulin aspart (2 zaug hauv ib hnub), yav tas los 1-2 zaug hauv ib hnub basal / pre / tus kheej sib xyaw, nrog / tsis muaj PHGP (N = 279).
Kev Hypoglycemia (1) 0.4, 0, 3.1 thiab 1.4%.
Kev Tshuaj Ntshav Siab (2) 49.8, 52.6, 66.1 thiab 73.5%.
Kev sib txuam
Muaj ntau tus yeeb tshuaj uas cuam tshuam rau kev xav tau cov tshuaj insulin.
Qhov kev xav tau rau cov kua dej tuaj yeem txo: qhov ncauj hypoglycemic tshuaj, glucagon-zoo li peptide-1 receptor agonists (GLP-1), MAO inhibitors, tsis xaiv-beta-blockers, ACE inhibitors, salicylates, anabolic steroids thiab sulfonamides.
Kev xav tau cov tshuaj insulin tuaj yeem nce ntxiv: qhov ncauj tshuaj hormonal contraceptives, thiazide diuretics, corticosteroids, cov thyroid hormones, sympathomimetics, somatropin thiab danazole.
Beta-blockers tuaj yeem npog cov tsos mob ntawm kev mob ntshav qab zib.
Octreotide / lanreotide tuaj yeem nce ntxiv thiab txo qis qhov xav tau ntawm lub cev.
Ethanol tuaj yeem ob qho tib si txhim kho thiab txo qis qhov kev tiv thaiv hypoglycemic ntawm insulin.
Qee cov tshuaj, thaum ntxiv rau qhov sib xyaw ua ke ntawm insulin degludec + insulin aspart, tuaj yeem ua rau kev puas tsuaj ntawm insulin degludec thiab / lossis insulin aspart. Kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart yuav tsum tsis txhob ntxiv rau kev daws teeb meem. Koj tsis tuaj yeem sib xyaw cov tshuaj no nrog lwm yam tshuaj.
Clinically kev sib cuam tshuam tseem ceeb ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart
Cov tshuaj uas yuav ua rau muaj kev pheej hmoo ntawm hypoglycemia:tshuaj tiv thaiv kab mob ACE inhibitors angiotensin II receptor blockers, disopyramides, fibrates, fluoxetine, MAO inhibitors pentoxifylline, pramlintide, propoxyphenedej qab ntsev somatostatin analogues (piv txwv li octreotide), sulfonamides, GLP-1 receptor agonists, dipeptidyl peptidase-4 inhibitors; sodium-dependent glucose transporter type 2 inhibitors (SGLT-2 inhibitors).
Nrog rau kev siv ua ke ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart nrog cov tshuaj no, qhov kev txo qhov koob tshuaj thiab nce ntxiv hauv kev ncua ntawm kev saib xyuas qib qabzib kuj yuav tsum muaj.
Cov tshuaj uas tuaj yeem txo cov nyhuv ntawm kev sib xyaw ntawm insulin degludec + insulin aspart (txo cov ntshav qabzib):atypical tshuaj tiv thaiv kab mob (olanzapine thiab clozapine), corticosteroids, danazol diuretics, estrogens, glucagon, isoniazid, nicotinic acid, tshuaj tiv thaiv qhov ncauj phenothiazines, progesterones (suav nrog rau qhov sib deev ntawm qhov ncauj), cov khoom tiv thaiv kab mob, somatropin, sympathomimetics (suav nrog salbutamol, epinephrine, terbutaline), cov thyroid hormones.
Nrog rau kev siv ua ke ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart nrog cov tshuaj no, yuav tsum tau ntxiv cov koob tshuaj thiab ntau zaus ntawm kev saib xyuas cov kua nplaum ntau ntxiv.
Cov tshuaj uas tuaj yeem ua rau ob leeg nce thiab txo qis kev cuam tshuam ntawm kev sib xyaw ntawm insulin degludec + insulin aspart (txo qis ntshav qab zib): cawv beta-blockers, clonidine, lithium ntsev. Pentamidine tej zaum yuav ua rau hypoglycemia, uas qee zaum tuaj yeem muaj tus mob hyperglycemia.
Nrog rau kev siv ua ke ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart nrog cov tshuaj no, kev hloov kho koob tshuaj thiab nce ntxiv hauv kev ncua ntawm kev saib xyuas qib qabzib yuav tsum muaj.
Cov tshuaj uas tuaj yeem npog qhov cim thiab cov tsos mob ntawm tus mob qog ntshav qab zib: beta blockers, clonidine, guanethidine thiab reserpine. Nrog rau kev siv ua ke ntawm kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart nrog cov tshuaj no, yuav tsum nce ntau zaus hauv kev saib xyuas cov kua nplaum ntau ntxiv.
Noj ntau dhau
Cov koob tshuaj tshwj xeeb uas ua rau kev txhaj tshuaj ntau dhau ntawm cov tshuaj insulin tsis tau tsim, tab sis hypoglycemia tuaj yeem tsim maj mam yog tias cov koob tshuaj ntau dhau piv rau tus neeg mob xav tau (saib "Kev Ceeb Toom"). Tus neeg mob tuaj yeem tshem tawm qhov mob ntshav qab zib me me los ntawm kev noj ntshav qab zib lossis cov khoom muaj suab thaj hauv qhov ncauj. Yog li, nws tau pom zoo rau cov neeg mob ntshav qab zib kom ua cov khoom qab zib tas li.
Yog tias qhov mob ntshav nce siab ntau, thaum tus neeg mob tsis nco qab lawm, nws yuav tsum txhaj tshuaj nrog glucagon (0.5 txog 1 mg) i / m lossis s / c (tuaj yeem ua haujlwm los ntawm tus neeg kawm tiav) lossis hauv / hauv dextrose (glucose) tov (tuaj yeem muab tau xwb tus neeg kho mob). Nws kuj tseem ceeb rau kev tswj hwm dextrose iv yog tias tus neeg mob tsis rov qab nco qab txog 10-15 feeb tom qab glucagon tswj. Tom qab nws rov qab nco qab, tus neeg mob tau qhia kom noj cov khoom noj uas muaj cov khoom noj carbohydrate kom tiv thaiv kom tsis txhob mob ntxiv ntshav qab zib.
Ceev faj ntawm cov tshuaj Insulin degludec + Insulin aspart
Kev ntshav siab. Yog tias koj hla ib pluas noj mov lossis ua kom lub cev tsis muaj zog txaus, tus neeg mob yuav muaj ntshav qab zib tsawg. Hypoglycemia tuaj yeem tsim kho yog tias qhov koob tshuaj insulin ntau dhau rau hauv kev sib raug zoo ntawm tus neeg mob cov kev xav tau (saib "Kev phiv los sis" thiab "Overdose").
Tom qab them nyiaj rau cov metabolism hauv kev noj haus (piv txwv li, kev siv tshuaj insulin ntau ntxiv), cov neeg mob cov tsos mob uas tshwm sim rau lawv tej zaum yuav hloov - cov mob ntshav sai ua ntej, hais txog qhov twg cov neeg mob yuav tsum tau ceeb toom. Cov tsos mob tshwm sim - cov uas qhia paub ua ntej yuav ploj thaum muaj ntshav qab zib ntev.
Cov kab mob tsis haum, tshwj xeeb tshaj yog kis thiab nrog kub taub hau, feem ntau ua rau lub cev xav tau cov tshuaj insulin. Koob tshuaj kuj tseem yuav tau ua yog tias tus neeg mob tau mob raum, mob siab, lossis qog rau lub qog, lub hlwb khiav, lossis lub qog.
Raws li nrog lwm yam kev npaj insulin los npaj lossis npaj nrog cov hauv paus pib, rov ua haujlwm tom qab hypoglycemia nrog kev sib xyaw ntawm insulin degludec + insulin aspart tej zaum yuav qeeb.
Muaj feem tshwm sim rau cov ntshav qog ntshav qab zib. Kev phom sij ntawm hypoglycemia nce nrog kev tswj hwm glycemic. Txoj kev pheej hmoo ntawm cov ntshav qog ntshav tom qab txhaj tshuaj yog cuam tshuam nrog lub sijhawm ntawm cov tshuaj insulin thiab feem ntau siab tshaj thaum cov piam thaj hauv cov ntshav ntawm insulin yog qhov siab tshaj plaws. Raws li tag nrho cov tshuaj insulin npaj, cov suab thaj-txo cov txiaj ntsig ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart yuav txawv nyob rau lub sijhawm ntawm cov neeg sib txawv lossis txawv sijhawm hauv tib tus neeg thiab nyob ntawm ntau yam mob, suav nrog thaj chaw txhaj, nrog rau cov ntshav thiab qhov kub ntawm qhov chaw txhaj tshuaj Cov.
Lwm yam uas tuaj yeem ua rau muaj kev pheej hmoo ntawm cov ntshav siab yog suav nrog kev hloov pauv ntawm kev noj zaub mov (piv txwv, cov ntsiab lus ntawm macronutrients lossis lub sijhawm noj mov), kev hloov pauv ntawm kev qoj ib ce, lossis hloov thaum noj ntawm qhov ncauj nrog lwm cov tshuaj (saib “Kev cuam tshuam”). Cov neeg mob raum lossis mob siab tsis txaus yuav ua rau muaj kev pheej hmoo siab ntau dua ntawm kev ua ntshav qab zib.
Cov tswv yim los txhawm rau txo qhov kev pheej hmoo ntawm hypoglycemia. Cov neeg mob thiab cov neeg zov me nyuam yuav tsum muaj peev xwm paub txog cov tsos mob ntawm tus mob ntshav qab zib thiab ua ntsuas kom tsim nyog. Kev tswj hwm tus kheej ntawm cov ntshav qab zib ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv thiab kho kev mob ntshav qab zib. Hauv cov neeg mob uas muaj kev pheej hmoo ntawm cov ntshav qog ntshav qab zib thiab hauv cov neeg mob uas tsis muaj peev xwm txo qis kev hnov mob ntshav qab zib, nce ntxiv rau ntawm kev saib xyuas ntshav qabzib tau pom zoo.
Qog Ntshav. Kev tsis txaus noj los sis tsis ncua kev kho mob tuaj yeem ua rau kev loj hlob ntawm hyperglycemia lossis ntshav qab zib ketoacidosis. Tsis tas li ntawd, cov kab mob sib kis, tshwj xeeb tshaj yog cov kis tau, tuaj yeem pab txhawb kev txhim kho hyperglycemic thiab, raws li, nce lub cev xav tau cov tshuaj insulin.
Raws li txoj cai, thawj cov tsos mob ntawm hyperglycemia tshwm sim maj, dhau ob peb teev lossis hnub. Cov tsos mob no suav nrog kev nqhis dej, tso zis sai, xeev siab, ntuav, nkees, liab thiab tawv nqaij ntawm daim tawv nqaij, qhov ncauj qhuav, tsis qab los noj mov, tsw ntxhiab tsw ntxhiab ntawm cov acetone hauv kev ua pa. Ntawm hom 1 mob ntshav qab zib mellitus, tsis muaj kev kho mob uas tsim nyog, hyperglycemia ua rau kev txhim kho mob ntshav qab zib ketoacidosis thiab tuaj yeem ua rau tuag taus.
Rau kev kho mob ntawm tus mob hyperglycemia, siv tshuaj tiv thaiv kab mob sai yog qhov pom zoo.
Hloov neeg mob los ntawm lwm cov tshuaj insulin. Kev hloov chaw ntawm tus neeg mob mus rau ib hom tshiab lossis npaj cov tshuaj insulin ntawm ib hom tshiab lossis lwm qhov chaw tsim khoom yuav tsum tshwm sim nyob rau hauv kev saib xyuas mob nkeeg nruj. Thaum txhais lus, yuav tau txhaj tshuaj kom haum.
Hyperglycemia lossis hypoglycemia nrog kev hloov pauv ntawm cov tshuaj insulin. Kev hloov pauv ntawm cov yam ntxwv ntawm insulin, chaw tsim tshuaj paus, hom lossis txoj kev tswj hwm yuav cuam tshuam rau kev tswj glycemic thiab kev xav ua rau hypoglycemia lossis hyperglycemia. Cov kev pauv no yuav tsum tau ua kom zoo zoo thiab tsuas yog nyob rau hauv kev saib xyuas ntawm tus kws kho mob, qhov ntau zaus ntawm kev ntsuas ntshav qabzib yuav tsum nce ntxiv. Rau cov neeg mob uas mob ntshav qab zib hom 2 mob ntshav qab zib, yuav tsum tau txhaj tshuaj kom haum nrog kev kho tus mob PHGP. Thaum hloov los ntawm lwm cov tshuaj insulin rau kev kho mob nrog kev sib xyaw ntawm insulin degludec + insulin aspart, nws yuav tsim nyog los kho qhov koob tshuaj.
Kev siv tshuaj ib txhij ntawm thiazolidinedione pab pawg thiab tshuaj insulin npaj. Cov kab mob ntawm kev txhim kho lub plawv tsis ua haujlwm tau qhia hauv kev kho mob ntawm cov neeg mob thiazolidinediones sib xyaw nrog kev npaj tshuaj insulin, tshwj xeeb tshaj yog tias cov neeg mob no muaj kev pheej hmoo ua rau lub plawv tsis ua haujlwm. Qhov tseeb no yuav tsum raug coj los txiav txim siab thaum cov neeg mob kho mob sib xyaw nrog thiazolidinediones thiab kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart. Nrog rau kev teem sijhawm ntawm txoj kev kho ua ke, nws yog ib qho tsim nyog yuav tsum ua kev soj ntsuam kev kho mob ntawm cov neeg mob kom paub cov cim thiab cov tsos mob ntawm lub plawv tsis ua hauj lwm, nce lub cev nyhav thiab muaj cov peripheral edema. Yog hais tias cov tsos mob ntawm lub plawv tsis zoo nyob rau hauv cov neeg mob, kev kho mob nrog thiazolidinediones yuav tsum tau tsum txiav.
Kev tuav cov dej hauv lub cev thiab kev loj hlob ntawm lub plawv tsis ua tiav nrog kev siv los ntawm gamma receptor agonists ua kom los ntawm peroxisome proliferator (peroxisome proliferator-qhib khoom receptor-gamma, PPAR gamma). Thiazolidinediones uas yog agonists PPARgamma yuav ua tau cov tshuaj tiv thaiv kom tsis haum lub cev, tshwj xeeb tshaj yog thaum siv ua ke nrog cov tshuaj insulin. Kev tuav cov dej hauv lub cev tuaj yeem ua rau qhov kev txhim kho lossis exacerbation ntawm chav kawm ntawm lub siab. Cov neeg mob tau txais insulin, suav nrog kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart, thiab agonists PPARgamma yuav tsum tau saib xyuas cov paib thiab cov tsos mob ntawm lub plawv tsis ua haujlwm. Yog tias CHF tshwm sim, nws yuav tsum tau ua kev kho mob raws li cov qauv kev kho mob tam sim no thiab txiav txim siab tsis ua ntxiv lossis txo qis koob tshuaj agonist PPARgamma.
Ua txhaum ntawm lub cev ntawm lub zeem muag. Kev siv tshuaj insulin ntau dua nrog kev txhim kho ntse hauv kev tswj hwm ntawm cov metabolism hauv cov roj ntsha tuaj yeem ua rau muaj kev tsis txaus siab nyob rau hauv cov xwm txheej ntawm tus mob ntshav qab zib retinopathy, thaum lub sij hawm ntev txhim kho hauv glycemic tswj txo qhov kev pheej hmoo ntawm kev mob ntshav qab zib retinopathy.
Kev tiv thaiv kev sib tsoo qhov tsis meej pem ntawm kev npaj tshuaj insulin. Tus neeg mob yuav tsum raug qhia cov ntawv cim ntawm daim ntawv lo ua ntej txhua yam kev txhaj tshuaj kom tsis txhob yuam kev tsis sib haum xeeb ntawm kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart nrog lwm cov tshuaj insulin. Cov neeg mob yuav tsum xyuas cov koob tshuaj ntawm lub khob tshuaj txhaj rau. Nws yog ib qho tsim nyog yuav tau qhia rau cov neeg mob dig muag lossis cov neeg muaj qhov muag tsis pom kev tias lawv ib txwm xav tau kev pab ntawm cov neeg tsis muaj teeb meem tsis pom kev thiab tau kawm los ua haujlwm nrog cov tshuaj txhaj.
Tshuaj tua kab mob rau cov tshuaj insulin. Thaum siv cov tshuaj insulin, kev tsim cov tshuaj tiv thaiv yog ua tau. Tsis tshua muaj teeb meem, kev tsim cov tshuaj tiv thaiv lub cev tuaj yeem xav kom muaj kev kho cov tshuaj insulin kom tiv thaiv cov mob ntawm hyperglycemia lossis hypoglycemia.
Kev Siv Tshuaj Tiv Thaiv Ib yam li tag nrho cov tshuaj tiv thaiv kab mob, kev tswj hwm insulin tuaj yeem ua rau kev tsim cov tshuaj tiv thaiv rau cov tshuaj insulin. Tshuaj tiv thaiv kab mob muaj peev xwm heev rau qhov rhiab heev thiab qhov tshwj xeeb ntawm cov kev tsom xam thiab yuav yog vim muaj ntau yam, xws li cov txheej txheem ntawm cov txheej txheem tsom xam, cov txheej txheem coj mus kuaj, cov qauv sau lub sijhawm, kev kho tus mob, thiab tus mob lwm yam. Rau cov laj thawj no, kev sib piv cov tshuaj tiv thaiv cov tshuaj tiv thaiv mus rau kev sib xyaw ua ke ntawm insulin degludec + insulin aspart nrog qib ntawm cov tshuaj tiv thaiv hauv lwm cov kev tshawb fawb lossis lwm yam tshuaj yeeb tuaj yeem ua kom yuam kev.
Hauv kev tshawb nrhiav hauv cov neeg mob uas muaj mob ntshav qab zib hom 1, 95.9% ntawm cov neeg mob tau txais kev sib xyaw ua ke ntawm insulin degludec + insulin aspart ib hnub ib zaug muaj kev kuaj pom zoo rau cov tshuaj tiv thaiv insulin tsawg kawg ib zaug thaum tshawb fawb, suav nrog 89% ntawm cov neeg mob uas nyuam qhuav pib qhov tshwm sim zoo, thaum 13% ntawm cov neeg mob no tsawg kawg 1 lub sijhawm thaum txoj kev tshawb fawb tau muab cov txiaj ntsig zoo rau cov tshuaj tiv thaiv rau insulin aspart, suav nrog 6.4% ntawm cov neeg mob uas tau txais txiaj ntsig zoo ntawm lub hauv paus. Hauv kev tshawb nrhiav hauv cov neeg mob uas muaj mob ntshav qab zib hom 2, 67.5% ntawm cov neeg mob tau txais kev sib xyaw ua ke ntawm insulin degludec + insulin aspart ib hnub ib zaug muaj cov txiaj ntsig zoo rau kev soj ntsuam ntawm cov tshuaj tiv thaiv rau insulin tsawg kawg 1 zaug hauv kev tshawb fawb, suav nrog 45.4% ntawm cov neeg mob leej twg muaj qhov txiaj ntsig zoo thaum pib ntawm txoj kev tshawb no, thaum 17.1% ntawm cov neeg mob no tsawg kawg 1 lub sijhawm ntawm kev kawm tshawb pom qhov zoo rau cov tshuaj tiv thaiv rau insulin aspart, suav nrog 12.3%, uas muaj cov txiaj ntsig zoo ntawm lub hauv paus. Cov tshuaj tiv thaiv kab mob ntshav siab ntau hauv kev kho mob ntshav qab zib hom 2 tej zaum yuav ua rau tsis txaus ntseeg vim muaj kev cuam tshuam nrog kev soj ntsuam vim muaj cov tshuaj insulin endogenous hauv cov qauv hauv cov neeg mob no. Lub xub ntiag ntawm cov tshuaj tiv thaiv uas cuam tshuam rau kev ua haujlwm hauv chaw kho mob yuav xav tau kom hloov cov koob tshuaj txhawm rau txhawm rau txhawm rau hloov zuj zus mus rau hyper- lossis hypoglycemia. Lub xub ntiag ntawm cov tshuaj tiv thaiv rau kev tiv thaiv degludec cov kua dej tsis tau tsim.
Hypersensitivity thiab kev ua xua. Kev tsis haum tshuaj loj rau lub neej, suav nrog anaphylaxis, tuaj yeem tsim kho nrog kev siv tshuaj insulin, suav nrog kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart. Hauv kev tiv thaiv kev mob siab, nws yog ib qho tsim nyog yuav tsum tsis txhob siv tshuaj sib xyaw ua ke ntawm insulin degludec + insulin aspart, kev kho mob raws li tus txheej txheem ntawm kev kho mob thiab saib xyuas kom txog thaum pom cov tsos mob thiab cov paib tau daws. Kev siv ntawm kev sib xyaw ua ke ntawm insulin degludec + insulin aspart yog contraindicated rau hauv cov neeg mob uas muaj qhov tsis haum lub zog tiv thaiv cov tshuaj insulin degludec lossis insulin aspart (saib "Contraindications").
Kev Hypokalemia. Txhua qhov insulins, suav nrog kev sib xyaw ua ke ntawm insulin degludec + insulin aspart, ua rau kev hloov pauv ntawm cov poov tshuaj los ntawm qhov chaw ntxiv rau hauv lub cell, uas tuaj yeem ua rau hypokalemia. Yog tsis kho hypokalemia tuaj yeem ua rau ua pa tuag tes tuag taw, ventricular arrhythmias, thiab kev tuag. Nws yog ib qho tsim nyog yuav tau soj ntsuam cov qib ntawm cov poov tshuaj hauv cov neeg mob uas muaj kev pheej hmoo ntawm hypokalemia, yog tias qhia (piv txwv li, cov neeg mob siv tshuaj uas txo cov poov tshuaj tsawg, ntxiv rau cov neeg mob noj tshuaj uas muaj kev cuam tshuam cov tshuaj potassium).
Cov pab pawg neeg tshwj xeeb
Cov neeg laus laus (tshaj 65 xyoos). Kev sib xyaw ua ke ntawm insulin degludec + insulin aspart tuaj yeem siv rau hauv cov neeg laus. Cov ntshav qabzib hauv lub ntsej muag yuav tsum tau ua tib zoo saib thiab cov tshuaj insulin hloov kho tus kheej (saib "Pharmacokinetics").
Siv hauv geriatrics. Hauv kev sim tshuaj, tag nrho cov 9 (2.5%) ntawm 362 cov neeg mob ntshav qab zib hom 1 uas raug kho nrog kev sib xyaw ntawm insulin degludec + insulin aspart yog 65 xyoo lossis laus dua thiab 4 (1.1%) yog 75 xyoo thiab lawm. Tag nrho ntawm 256 (25.7%) ntawm 998 tus neeg mob ntshav qab zib hom 2 uas siv cov tshuaj insulin degludec + insulin aspart yog 65 xyoo lossis laus dua thiab 32 (3.2%) yog 75 xyoo lossis laus dua. Kev sib piv sib piv tsis tau qhia pom qhov sib txawv ntawm kev nyab xeeb lossis kev ua tau zoo rau cov neeg mob uas muaj hnub nyoog 65 xyoos piv nrog cov neeg mob hluas.
Txawm li cas los xij, thaum siv nyob rau hauv cov neeg mob geriatric, kev ceev faj ntau dua yuav tsum tau siv, vim tias kev nkag siab ntau dua rau cov kev cuam tshuam ntawm kev sib xyaw ntawm insulin degludec + insulin aspart hauv qee tus neeg laus tsis tuaj yeem txiav txim siab. Thawj koob tshuaj, kev noj tshuaj ntau ntxiv thiab cov tshuaj txij nkawm yuav tsum tau muab ua zoo kom tsis txhob mob ntshav qab zib. Kev mob ntshav qab zib yog ib yam nyuaj yuav paub txog cov neeg laus.
Cov neeg mob uas lub raum tsis zoo thiab lub cev muaj zog. Kev sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart tuaj yeem siv rau hauv cov neeg mob uas lub raum tsis zoo thiab lub siab ua haujlwm. Cov ntshav qabzib hauv lub ntsej muag yuav tsum tau ua tib zoo saib thiab cov tshuaj insulin hloov kho tus kheej (saib "Pharmacokinetics").
Tsis hlauv. Hauv kev sim tshuaj, tag nrho ntawm 18 (5%) cov neeg mob ntshav qab zib hom 1 uas tau txais kev sib xyaw ntawm insulin degludec + insulin aspart muaj GFR tsawg dua 60 ml / min / 1.73 m 2 lossis tsawg dua hauv 1 (0.3%) tus neeg mob GFR tsawg dua 30 ml / min / 1.73 m 2 lossis tsawg dua. Tag nrho ntawm 111 (11%) ntawm 998 cov neeg mob uas muaj ntshav qab zib hom 2 uas tau txais kev sib xyaw ntawm insulin degludec + insulin aspart muaj GFR tsawg dua 60 ml / min / 1.73 m 2, thiab tsis muaj ib tus neeg mob tau GFR tsawg dua 30 ml / feeb / 1.73 m 2.
Tsis muaj qhov sib txawv hauv cov pharmacokinetics ntawm cov tib neeg sib xyaw ua ke ntawm cov tshuaj sib xyaw ua ke ntawm insulin degludec + insulin aspart ntawm kev tshawb fawb autonomous thaum piv rau cov neeg muaj kev noj qab haus huv thiab cov neeg muaj lub raum tsis ua haujlwm. Txawm li cas los xij, zoo ib yam li txhua qhov insulins, hauv cov neeg mob lub raum tsis txaus, kev saib xyuas ntshav qabzib yuav tsum ua kom zoo dua, thiab kev noj cov tshuaj insulin degludec + insulin aspart sib xyaw yuav tsum tau kho nyob ntawm tus kheej.
Daim siab ua haujlwm. Tsis muaj qhov sib txawv hauv cov pharmacokinetics ntawm cov tib neeg sib xyaw ua ke ntawm cov tshuaj insulin degludec + insulin aspart ntawm kev tshawb fawb autonomous thaum piv rau cov kev kawm muaj kev noj qab haus huv thiab cov ncauj lus nrog daim siab tsis ua haujlwm (mob me, mob hnyav thiab mob siab tsis ua haujlwm). Txawm li cas los xij, ib yam li nrog tag nrho cov insulins, kev kuaj xyuas ntshav qab zib yuav tsum tau ua kom zoo dua qub thiab kev noj tshuaj ntawm cov tshuaj insulin degludec + insulin aspart kev sib xyaw ua ke hloov kho ntawm tus kheej hauv cov neeg mob uas muaj lub siab tsis zoo.
Menyuam yaus thiab tub ntxhais hluas. Cov ntaub ntawv pharmacokinetic uas twb muaj lawm tau nthuav tawm hauv ntu Pharmacokinetics, txawm li cas los xij, qhov kev ua tau zoo thiab kev nyab xeeb ntawm kev sib xyaw ntawm cov tshuaj insulin degludec + insulin aspart hauv cov menyuam yaus thiab cov tub ntxhais hluas hnub nyoog qis dua 18 xyoo tsis tau kawm, cov lus pom zoo rau cov koob tshuaj ntawm cov menyuam tsis tau tsim.
Tsis txhob hloov tus xaum xim rau lwm tus neeg mob. Tus cwj mem yuav tsum tsis txhob raug hloov mus rau lwm tus neeg, txawm tias lub koob tau hloov. Kev siv tus cwj mem ib leeg los ntawm lwm tus neeg mob ua rau muaj kev pheej hmoo kis tus mob hematogenous.
Cuam tshuam rau kev muaj peev xwm tsav tsheb thiab tshuab. Lub peev xwm ntawm cov neeg mob kom pom tseeb thiab qhov tshuaj tiv thaiv yuav ua rau lub sijhawm tsis muaj ntshav qab zib, uas tuaj yeem tsim kev puas tsuaj rau qhov xwm txheej no qhov tshwj xeeb tshaj yog tsim nyog (piv txwv, thaum tsav tsheb lossis ua haujlwm nrog tshuab).
Cov neeg mob yuav tsum qhia rau kev ntsuas kom tiv thaiv kev txhim kho hypoglycemia thaum tsav tsheb.Qhov no yog qhov tseem ceeb tshwj xeeb tshaj yog rau cov neeg mob tsis tuaj lossis cov tsos mob ploj zuj zus - ua ntej ntawm kev txhim kho hypoglycemia lossis nrog kev mob tshwm sim tsis tu ncua ntawm hypoglycemia. Hauv cov rooj plaub no, qhov tsim nyog ntawm kev tsav tsheb yuav tsum xav txog.
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Hom kev kuaj mob, txheej txheem ntawm lawv cov txheej txheem, kev taw qhia rau kev siv
Kev ntxuav tawm hauv qhov quav Kev siv tshuaj ntxuav kom zoo nkauj yog siv los ntxuav txoj hnyuv quav thiab quav. Qhov tshuaj ntxuav tawm tsuas yog ua kom qis qis ntawm txoj hnyuv. ... -
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