Cov tshuaj Baeta: tshuaj xyuas cov kws tshaj lij thiab cov chaw tsim khoom, cov nqi

Cov tshuaj yog tshuaj rau hom 2 mob ntshav qab zib mellitus rau kev kho ntxiv rau:

• thiazolidinedione,
• metformin
• sulfonylurea derivative,
• kev sib xyaw ua ke ntawm sulfonylurea, metformin thiab ib qho derivative,
• kev sib txuas ntawm thiazolidinedione thiab metformin,
• los yog thaum tsis muaj kev tswj hwm glycemic txaus.

Kev noj tshuaj ntxiv

Bayeta yog subcutaneously muab rau hauv tus ncej puab, caj npab los yog plab. Thawj koob tshuaj yog 5 mcg. Nkag mus 2 zaug ntawm ib hnub txog 1 teev ua ntej noj tshais thiab noj hmo. Tom qab noj mov, cov tshuaj yuav tsum tsis txhob siv tshuaj.

Yog hais tias tus neeg mob rau qee yam tau hla lub luag haujlwm ntawm kev siv tshuaj, ntxiv kev txhaj tshuaj tshwm sim tsis hloov. Tom qab ib hlis ntawm kev kho mob, thawj qhov kev pib siv tshuaj yuav tsum tau nce rau 10 mcg.

Nrog rau kev tswj hwm ib txhij ntawm Bayet nrog thiazolidinedione, metformin, lossis nrog kev sib xyaw ntawm cov tshuaj no, thawj koob tshuaj thiazolidinedione lossis metformin tsis tuaj yeem hloov pauv.

Yog tias koj siv kev sib xyaw ntawm Baeta nrog sulfonylurea derivatives (txhawm rau txo qis kev pheej hmoo ntawm hypoglycemia), koj yuav tsum tau txo qis dua ntawm sulfonylurea derivative.

Daim ntawv thov nta

• cov tshuaj yuav tsum tsis txhob siv tshuaj tom qab noj mov tas,
• kev qhia ntawm cov tshuaj IM lossis IV tsis pom zoo,
• cov tshuaj yuav tsum tsis txhob siv yog tias txoj kev daws teeb meem lossis huab,
• Bayetu yuav tsum tsis txhob raug tswj hwm yog tias cov khoom tau pom hauv qhov kev daws teeb meem,
• tawm tsam keeb kwm ntawm kev kho rau exenatide, cov tshuaj tiv thaiv kab mob yog ua tau.

Tseem Ceeb! Hauv ntau tus neeg mob uas nws lub cev tsim cov tshuaj tiv thaiv, titer poob qis thiab kev kho mob tseem qis rau 82 lub lis piam raws li kev kho mob txuas ntxiv. Txawm li cas los xij, qhov tseem ceeb ntawm cov tshuaj tiv thaiv tsis cuam tshuam rau cov hom thiab zaus ntawm cov kev mob tshwm sim.

Tus kws kho mob uas koom nrog yuav tsum qhia nws tus neeg mob tias kev kho nrog Bayeta yuav ua rau kom nws tsis qab los, thiab lub cev hnyav. Qhov no yog tus nqi pheej yig piv rau cov txiaj ntsig ntawm kev kho mob.

Hauv kev sim ua ntej uas tau ua dhau los ntawm nas thiab nas nrog cov nyhuv carcinogenic thaum txhaj nrog tshuaj exenatide, nws tsis pom.

Thaum ib koob ntawm 128 lub sij hawm tib neeg koob tshuaj tau raug kuaj hauv cov nas, nas tau pom tias muaj ntau qhov kev ua tau zoo (tsis muaj kev cuam tshuam ntawm kev muaj mob tsis zoo) ntawm cov thyroid C-cell adenomas.

Cov kws tshawb fawb tau muab qhov tseeb no piv rau qhov nce ntawm lub neej ntawm kev sim cov tsiaj uas tau txais exenatide. Tsis tshua muaj, tab sis txawm li cas los xij muaj kev ua txhaum ntawm lub raum ua haujlwm. Lawv suav nrog

• kev tsim kho raum tsis ua haujlwm,
• kom ntshiab si creatinine,
• kev tsim txom ntawm cov chav kawm ntawm mob mob ntsws thiab mob raum tsis zoo, uas feem ntau yuav tsum tau mob hemodialysis.

Qee qhov kev pom no tau pom hauv cov neeg mob uas tau siv ib lossis ntau yam tshuaj tib lub sijhawm uas cuam tshuam rau cov dej metabolism, lub raum ua haujlwm, lossis lwm yam kev hloov pauv hauv lub neej.

Cov tshuaj txuam nrog muaj NSAIDs, ACE inhibitors, thiab tshuaj tso ntshav. Thaum sau tshuaj kho cov tsos mob thiab tshem tawm cov tshuaj, uas yog txawm tias yog qhov ua rau ntawm cov txheej txheem pathological, hloov kho lub raum ua haujlwm tau rov qab los.

Tom qab ua qhov kev tshawb fawb hauv chav kho mob thiab preclinical, exenatide tsis tau qhia cov pov thawj ntawm nws cov nephrotoxicity ncaj qha. Tawm tsam cov keeb kwm yav dhau los ntawm kev siv tshuaj Bayeta, cov tsis tshua muaj tshwm sim ntawm tus mob pancreatitis tau tshwm sim.

Thov nco tseg: Cov neeg mob yuav tsum paub txog cov tsos mob ntawm tus mob pancreatitis. Thaum sau daim ntawv kho cov tsos mob, kev kho mob tshwm sim ntawm txoj kev mob ntawm tus txiav ntawm lub txiav.

Ua ntej pib kev txhaj tshuaj ntawm Bayeta, tus neeg mob yuav tsum nyeem cov lus qhia txuas nrog siv tus cwj mem syringe, tus nqi kuj tseem qhia nyob rau ntawd.

Cov Yuav Tsum Muaj

1. Qhov muaj ntshav qab zib ketoacidosis.
2. Yam 1 ntshav qab zib.
3. Cev xeeb tub
4. Lub xub ntiag ntawm cov mob hnyav plab zom mov.
5. Mob raum tsis ua haujlwm.
6. Kev pub niam mis.
7. Lub hnub nyoog txog 18 xyoo.
8. Hypersensitivity rau lub Cheebtsam ntawm cov tshuaj.

Cev xeeb tub thiab pub niam mis

Hauv ob qho ntawm cov sijhawm no, cov tshuaj yog contraindicated. Tus nqi ntawm ib tus cwj pwm tsis haum rau qhov kev pom zoo no tej zaum yuav dhau lawm. Nws raug paub tias ntau yam tshuaj muaj yeeb tshuaj tsis zoo cuam tshuam kev loj hlob ntawm lub me nyuam hauv plab.

Leej niam tsis quav ntsej lossis tsis quav ntsej ua rau tuaj yeem tuaj yeem ua rau me nyuam hauv plab tsis zoo. Yuav luag txhua cov tshuaj nkag rau hauv tus menyuam lub cev nrog niam cov kua mis, yog li cov tshuaj no yuav tsum tau ceev faj txhua yam tshuaj.

Kev Kho Mob Kho Mob

Cov kev phiv tshuaj uas tau pom nyob hauv cov neeg mob ntau dua ib zaug tau teev muaj npe hauv qab no:

Cov tshuaj tiv thaiv hauv zos:

• Feem ntau qhov khaus tshwm sim ntawm thaj chaw txhaj tshuaj.
• Tsis tshua muaj, liab thiab tawm pob.

Ntawm ib feem ntawm lub plab zom mov, cov tsos mob hauv qab no feem ntau pom:

Lub hauv nruab nrab cov leeg hlwb feem ntau cuam tshuam nrog kiv taub hau. Yog tias peb sib piv cov tshuaj Bayeta nrog cov placebo, tom qab ntawd qhov xwm txheej ntawm cov neeg mob ntshav qab zib hauv qhov tshuaj piav qhia tau siab dua 4%. Kev siv ntawm lub phaum ntawm lub qog ntshav qab zib yog yam ntxwv tsis tshua hnyav lossis hnyav.

Kev sib txuas ua ke

Cov xwm txheej tsis zoo uas tau pom hauv cov neeg mob ntau dua ib zaug nrog kev sib xyaw ua ke yog qhov zoo ib yam li cov kev kho mob monotherapy (saib cov lus saum toj no).

Lub plab zom mov teb:

1. Feem ntau: tsis qab los noj mov, xeev siab, ntuav, raws plab, hloov plab zom mov, dyspepsia.
2. Kev paub tab: tsam plab thiab mob plab, cem quav, sib duav, pom kev, ua txhaum, saj ntawm saj.
3. Tsis tshua muaj: mob mob leeg qhuav nrog.

Feem ntau, hnov ​​xeev siab txog qib nrab lossis qaug zog qhov zoo yog soj ntsuam. Nws yog qhov txaus siab txo qis thiab txo qis dhau sijhawm tsis muaj kev cuam tshuam cov haujlwm txhua hnub.

Lub hauv nruab nrab cov hlab hlwb feem ntau cuam tshuam nrog mob taub hau thiab kiv taub hau, tsis tshua muaj nrog tsaug zog.

Ntawm ib feem ntawm cov kab mob endocrine, kev mob ntshav qab zib yog feem ntau pom yog tias exenatide muab tso nrog sulfonylurea derivatives. Raws li qhov no, nws yog ib qho tsim nyog los tshuaj xyuas cov tshuaj sulfonylurea derivatives thiab txo lawv nrog kev pheej hmoo ntawm kev mob ntshav qab zib.

Feem ntau ntawm cov hypoglycemic lub sijhawm uas nws nyob rau hauv kev siv yog tus yam ntxwv me thiab hauj sim. Koj tuaj yeem cheem cov kev ua kom tsuas yog los ntawm qhov ncauj siv cov carbohydrates. Ntawm ib feem ntawm cov metabolism, thaum noj cov tshuaj Bayeta, hyperhidrosis tuaj yeem pom, ntau zaus lub cev qhuav dej yog txuam nrog ntuav lossis zawv plab.

Cov kab mob zis hauv cov neeg mob tsis tshua haum nrog lub raum tsis ua haujlwm thiab mob nyuaj.

Kev txheeb xyuas pom tias kev fab tshuaj muaj qhov tsis haum. Qhov no yuav yog duab zas los yog kev kuaj mob anaphylactic.

Cov tshuaj tiv thaiv hauv zej zog thaum txhaj tshuaj sab nraub qaum suav nrog ua pob liab liab, liab thiab khaus ntawm qhov chaw txhaj tshuaj.

Muaj kev tshuaj xyuas cov teebmeem ntawm kev nce qib erythrocyte sedimentation (ESR). Qhov no ua tau yog tias nce tawm tau siv tib lub sijhawm nrog warfarin. Xws li qhov tsis tshua pom tshwm sim tuaj yeem los nrog los ntshav.

Yeej, cov kev mob tshwm sim tau me me los yog mob nyhav, uas tsis tas yuav tsum tsis ua hauj lwm txog kev kho mob.

Kws Tshuaj

Pharmacological kev txiav txim - hypoglycemic, incretinomimetic.

Cov nce ntxiv, xws li glucagon-zoo li peptide-1 (GLP-1), txhim kho kev ua haujlwm ntawm beta hlwb, txhim kho cov kua nplaum tsis txaus-tso cov kua dej tsis txaus, txwv tsis pub muaj ntshav qabzib ntau thiab ua rau lub plab zom mov tom qab lawv nkag mus rau hauv cov ntshav tawm ntawm txoj hnyuv. Exenatide yog lub zog loj zuj zus uas ua rau cov ntshav qabzib ntau yam tso tsis tau zoo ntawm cov insulin thiab muaj lwm yam teebmeem ntshav qab zib ntau ntau rau qhov ua kom nce zuj zus, uas txhim kho glycemic tswj hauv cov neeg mob ntshav qab zib hom 2.

Cov amino acid sib lawv liag ntawm exenatide qee leej sib luag nrog cov kab xaj ntawm tib neeg GLP-1. Exenatide tau pom tias yuav khi thiab ua kom GLP-1 cov neeg tau txais hauv tib neeg hauv vitro, uas ua rau cov ntshav qabzib ntau nyob ntawm cov tshuaj tua kab mob insulin thiab, hauv vivo, rau lub zais ntawm cov tshuaj insulin los ntawm pancreatic beta hlwb nrog kev koom tes ntawm cyclic AMP thiab / lossis lwm yam kev cuam tshuam ntawm cov pa.

Exenatide txhim kho glycemic tswj hauv cov neeg mob uas muaj ntshav qab zib hom 2 los ntawm ob peb lub tshuab.

Hauv hyperglycemic tej yam kev mob, exenatide ua rau cov piam thaj tsis muaj peev xwm tso cov kua dej ntawm cov kua dej los ntawm pancreatic beta hlwb. Qhov insulin secretion tso tseg thaum cov concentration ntawm cov piam thaj hauv cov ntshav txo qis thiab nws nce mus rau qhov qub, yog li txo cov kev pheej hmoo ntawm cov ntshav qog ntshav qab zib.

Cov tshuaj insulin tso tawm thaum thawj 10 feeb, hu ua "thawj theem ntawm cov tshuaj insulin", tsis tuaj rau cov neeg mob ntshav qab zib hom 2. Tsis tas li ntawd, qhov poob ntawm thawj theem ntawm cov tshuaj insulin yog ib qho kev ua tsis tau zoo thaum pib ntawm beta-cell ua haujlwm hauv ntshav qab zib hom 2. lossis txhim kho ntau dua ob qho theem ib thiab theem thib ob ntawm insulin teb rau hauv cov neeg mob uas muaj ntshav qab zib hom 2.

Hauv cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus tawm tsam keeb kwm ntawm hyperglycemia, kev coj noj coj ua ntawm exenatide txwv kev tso cia ntau dhau ntawm glucagon. Txawm li cas los xij, exenatide tsis cuam tshuam rau lub cev glucagon teb li cas rau kev mob ntshav qab zib.

Nws tau pom tias kev tswj hwm ntawm exenatide ua rau muaj kev poob qis thiab ua kom muaj zaub mov noj tsawg ntxiv (hauv tsiaj thiab tib neeg).

Hauv cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus, kev kho mob exenatide nrog kev sib xyaw nrog metformin thiab / lossis sulfonylurea kev npaj ua rau txo qis ntshav qabzib, postprandial ntshav qabzib, thiab glycosylated hemoglobin index (HbA1c), yog li txhim kho glycemic tswj hauv cov neeg mob no.

Carcinogenicity, mutagenicity, muaj kev cuam tshuam ntawm kev muaj menyuam

Hauv kev kawm txog cov carcinogenicity ntawm exenatide hauv cov nas thiab nas, nrog sc kev tswj hwm ntawm kev noj tshuaj ntawm 18, 70 thiab 250 μg / kg / hnub, kev nce lej ntawm C-cell cov thyroid adenomas tsis muaj cov cim tsis zoo hauv cov nas tsuag tau raug sau tseg ntawm txhua koob tshuaj kawm (5 , 22 thiab 130 npaug siab dua MPD hauv tib neeg). Hauv cov nas, tswj hwm ntawm tib lub tshuaj tsis tau qhia tawm cov nyhuv carcinogenic.

Mutagenic thiab clastogenic cov teebmeem ntawm exenatide thaum lub sijhawm ua kev sim ntau yam tsis pom.

Hauv kev tshawb fawb txog kev muaj menyuam hauv cov nas, hauv cov pojniam tau txais qhov koob tshuaj 6, 68 lossis 760 mcg / kg / hnub, pib txij li 2 lub lis piam ua ntej pib sib deev thiab tsis pub dhau 7 hnub ntawm cev xeeb tub, tsis muaj qhov tshwm sim zoo rau tus menyuam hauv koob rau txog 760 mcg / kg / hnub (cov tshuaj tiv thaiv ib puag ncig yog nce mus txog 390 lub sijhawm siab dua MPRD - 20 mcg / hnub, xam los ntawm AUC).

Xuas. Tom qab sc tswj kev ua haujlwm ntawm exenatide ntawm ib koob ntawm 10 μg rau cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus, exenatide nrawm nrawm dua, Cmax (211 pg / ml) tau tiav tom qab 2.1 teev. AUCo-inf yog 1036 pg · h / ml. Exenatide raug nthuav dav (AUC) nce nce raws feem ntau ntawm cov koob tshuaj ntau npaum li cas ntawm 5 txog 10 μg, thaum tsis muaj qhov sib luag ntawm Cmax. Tib cov txiaj ntsig tau pom nrog kev coj ua subcutaneous ntawm exenatide hauv plab, ncej puab lossis caj npab.

Kev faib khoom .Vd ntawm exenatide tom qab ib qho kev tswj hwm sc nkaus xwb yog 28.3 L.

Kev ntsuas phoo thiab nthuav tawm. Nws yog dhau los feem ntau los ntawm glomerular pom ua raws los ntawm kev muaj proteolytic degradation. Exenatide tshem tawm yog 9.1 l / h. Qhov kawg T1 / 2 yog 2.4 teev. Cov tshuaj uas txawv ntawm exenatide yog koob tshuaj ywj siab. Ntsuas qhov ntau ntawm exenatide raug txiav txim kwv yees li 10 teev tom qab noj tshuaj.

Pharmacokinetics hauv cov chaw kuaj mob tshwj xeeb

Lub raum khiav tsis zoo. Hauv cov neeg mob uas mob raum me los sis mob raum (Cl creatinine 30-80 ml / min), kev kis mob exenatide tsis txawv ntawm qhov ntawd hauv cov neeg mob uas lub raum tsis ua haujlwm zoo. Txawm li cas los xij, nyob rau hauv cov neeg mob uas mob raum tsis ua haujlwm rau lub raum lim ntshav, qhov kev sib kis tau nce siab dua 3.37 npaug dua hauv cov ntsiab lus zoo.

Lub siab ua haujlwm tsis zoo. Pharmacokinetics cov kev tshawb fawb hauv cov neeg mob uas muaj lub siab los yog mob siab tsis ua haujlwm tsis tau ua.

Kwv Txhiaj. Cov chaw muag tshuaj ntawm exenatide hauv cov neeg sawv cev ntawm ntau haiv neeg sib txawv tsis hloov.

Lub Cev Ntsuas Qhov Loj (BMI). Cov pejxeem tsom tshuaj pharmacokinetic nyob rau hauv cov neeg mob uas muaj BMI ntawm ≥30 kg / m2 thiab Exenatide

Hom 2 mob ntshav qab zib mellitus ua cov tshuaj ntxiv rau kev kho mob nrog metformin, sulfonylurea derivative, thiazolidinedione, kev sib xyaw ntawm metformin thiab sulfonylurea derivative, lossis kev sib xyaw ntawm metformin thiab thiazolidinedione thaum tsis muaj glycemic tswj tsis tau.

Phiv cov tshuaj tiv thaiv Exenatide

Siv nrog metformin thiab / lossis sulfonylurea derivative

Lub rooj qhia txog cov kev tsis zoo (tshwj tsis yog rau ntshav ntshav) uas tshwm sim nrog ib qho zaus ntawm frequency5% thiab dhau ntawm cov placebo uas tau sau tseg hauv peb 30 lub lis piam tswj kev sim ntawm exenatide ntxiv rau metformin thiab / lossis sulfonylurea derivative.

Cov kev mob tshwm sim pom nrog qhov zaus ntawm> 1%, tab sis Kev Sib Hloov

Exenatide yuav tsum siv nrog ceeb toom rau cov neeg mob noj tshuaj uas yuav tsum tau nqus sai los ntawm kev mob plab, nws tuaj yeem ncua plab zom mov. Cov neeg mob yuav tsum raug qhia kom noj cov tshuaj hauv qhov ncauj, cov nyhuv ntawm nws nyob ntawm lawv lub luag haujlwm tseem ceeb (piv txwv li tshuaj tua kab mob), tsawg kawg 1 teev ua ntej kev tswj hwm ntawm exenatide. Yog tias cov tshuaj no yuav tsum tau noj nrog zaub mov, tom qab ntawd lawv yuav tsum noj thaum cov zaub mov noj thaum cov tshuaj exenatide tsis tau txais.

Digoxin. Nrog kev tswj hwm tib lub sijhawm ntawm digoxin (ntawm koob tshuaj 0.25 mg 1 zaug / hnub) nrog exenatide (10 μg 2 zaug hauv ib hnub), Cmax ntawm digoxin txo qis li 17%, thiab Tmax nce tau ntev li 2.5 teev. Txawm li cas los xij, tag nrho cov tshuaj pharmacokinetic nyhuv (AUC) hauv lub xeev nyiaj tsis kho tsis tau hloov.

Lovastatin. Nrog rau ib koob tshuaj lovastatin (40 mg) thaum noj cov tshuaj exenatide (10 μg 2 zaug hauv ib hnub), AUC thiab Cmax ntawm lovastatin txo los ntawm kwv yees li 40 thiab 28%, feem, thiab Tmax tau nce ntxiv los ntawm 4 teev. Hauv 30 lub sijhawm tswj kev tshawb fawb hauv tsev kho mob, exenatide tau muab rau cov neeg mob twb tau txais HMG-CoA reductase inhibitors tsis tau nrog cov kev hloov hauv lipid muaj pes tsawg leeg cov ntshav.

Lisinopril. Hauv cov neeg mob uas mob me me los sis mob me ntawm cov roj ntsha muaj zog los ntawm lisinopril (5-20 mg / hnub), exenatide tsis hloov pauv ntawm AUC thiab Cmax ntawm lisinopril hauv kev sib npaug. Tmax ntawm lisinopril ntawm qhov sib npaug nce los ntawm 2 teev Tsis tau muaj qhov hloov pauv ntawm qhov ntsuas ntawm nruab nrab txhua hnub SBP thiab DBP.

Warfarin. Hauv kev tswj xyuas cov kev sim mob hauv cov neeg tuaj yeem noj qab haus huv, nws tau sau tseg tias nrog kev qhia txog warfarin 30 feeb tom qab exenatide, Tmax ntawm warfarin tau nce li 2 teev. Nyob rau lub sijhawm ntawm kev soj ntsuam tom qab tshaj tawm, ntau kis ntawm kev nce INR tau tshaj tawm, qee zaum nrog los ntshav nrog kev siv exenatide nrog warfarin (kev saib xyuas ntawm PV yog qhov tsim nyog, tshwj xeeb tshaj yog thaum pib kho thiab thaum hloov cov tshuaj).

Kev siv exenatide txuam nrog insulin, D-phenylalanine derivatives, meglitinides lossis alpha-glucosidase inhibitors tsis tau kawm.

Ceevfaj Exenatide

Vim tias qhov tseeb tias qhov tsawg zaus ntawm kev txo ntshav qab zib nce nrog kev sib koom tes ntawm kev sib koom tes ntawm exenatide nrog sulfonylurea derivatives, nws yog qhov tsim nyog los muab rau txo qis ntawm koob tshuaj sulfonylurea derivatives nrog kev pheej hmoo ntawm hypoglycemia. Feem ntau qhov tshwm sim ntawm cov ntshav qog nqaij hlav hauv qhov sib luag tau mob me me los yog mob nyhav thiab raug tso tseg los ntawm kev noj zaub mov hauv qhov ncauj.

Nws tsis pom zoo hauv / hauv lossis hauv / m tswj hwm ntawm cov tshuaj.

Nyob rau lub sijhawm ntawm kev soj ntsuam tom qab tshaj tawm, cov xwm txheej tsis tshua muaj tshwm sim ntawm kev loj hlob ntawm tus mob leeg qhuav hauv cov neeg mob noj exenatide tau sau tseg. Cov neeg mob yuav tsum tau qhia paub tias kev mob plab ntev ntev, uas tuaj yeem nrog ntuav, yog tus mob ntawm pancreatitis. Yog tias muaj kev ua xyem xyav ntawm kev tsim tus mob pancreatitis, exenatide lossis lwm qhov kev xav tias cov tshuaj yuav tsum tsis ua ntxiv lawm, kev tshuaj xyuas kab mob yuav tsum tau ua, thiab kev kho tsim nyog yuav tsum tau pib. Yog tias kev kuaj mob ntawm tus kab mob pancreatitis tau lees paub, kev rov ua dua ntawm kev kho mob nrog exenatide tsis pom zoo yav tom ntej.

Thaum lub sijhawm kev soj ntsuam tom qab muag, muaj qee qhov tsis pom kev tsis nco qab lub raum kev ua haujlwm tau sau tseg, suav nrog cov tshuaj muaj zog ntau ntxiv, zuj zus ntxiv hauv kev mob raum tsis ua haujlwm, mob raum tsis ua haujlwm, qee zaum yuav tsum muaj mob hemodialysis. Qee qhov xwmtxheej no tau sau tseg rau cov neeg mob uas tau siv ib lossis ntau yam tshuaj uas paub zoo txog lub raum ua haujlwm thiab / lossis cov neeg mob uas xeev ntuav, ntuav thiab / lossis zawv plab nrog / tsis muaj dej, thaum siv tshuaj, suav nrog Cov. ACE inhibitors, NSAIDs, tshuaj tso ntshav qab zib. Lub raum tsis zoo muaj peev xwm thim rov qab nrog kev kho kev kho mob thiab kev tshem tawm yeeb tshuaj, muaj feem cuam tshuam rau lub raum kev ua haujlwm, suav nrog exenatide. Hauv kev kawm ua ntej thiab kev soj ntsuam, exenatide tsis tau qhia ncaj qha nephrotoxicity.

Antibodies rau exenatide tuaj yeem tshwm sim thaum kev kho mob nrog exenatide.

Cov neeg mob yuav tsum paub tias kev kho mob nrog exenatide tuaj yeem ua rau poob qab los noj mov thiab / lossis lub cev qhov hnyav thiab tias vim muaj cov teebmeem no tsis tas yuav hloov pauv kev noj tshuaj.

Xov Xwm Lwm Yam

• Exenatide (exenat> Daim Ntawv Thov Nta

Cov tshuaj yog muab tshuaj subcutaneously nyob rau sab sauv los yog nruab nrab thib peb ntawm lub xub pwg, ncej puab, thiab tseem nyob hauv plab. Raws li txoj cai, nws raug nquahu kom hloov rau cov chaw no kom tsis txhob muaj kev tsim cov khoom lag luam subcutaneous.

Kev txhaj tshuaj yuav tsum tau ua kom raug raws li txhua txoj cai siv rau kev xaum xim. Cov tshuaj yuav tsum tau siv sijhawm ib teev ua ntej cov zaub mov tseem ceeb ntawm lub sijhawm tsawg kawg 6 teev.

Exenatide tsis tuaj yeem tov nrog lwm cov ntaub ntawv tshuaj, uas yuav zam qhov kev txhim kho ntawm cov kev tsis haum siab.

Muaj pes tsawg leeg ntawm BAETA

Kev daws rau sc tswj hwm yog tsis muaj xim, pob tshab.

Cov muaj mob: sodium acetate trihydrate, glacial acetic acid, mannitol, metacresol, dej rau thiab.

1.2 ml - syringe cwjmem (1) - pob khoom los ntawm cardboard (1).
2.4 ml - xaum npai (1) - pob khoom los ntawm cardboard (1).

Kev siv tshuaj hypoglycemic. Glucagon-zoo li Peptide Receptor Agonist

Kev siv tshuaj hypoglycemic. Exenatide (Exendin-4) yog qhov ua kom zoo ntxiv thiab yog 39-amino acid amidopeptide. Cov tshuaj tsis sib xws, xws li glucagon-zoo li peptide-1 (GLP-1), txhim kho cov kua dej tsis txaus rau cov insulin secretion, txhim kho β-cell muaj nuj nqi, txwv tsis pub muaj ntshav qabzib ntau thiab ua rau lub plab zom mov tom qab lawv nkag mus rau hauv cov ntshav tawm ntawm txoj hnyuv. Exenatide yog lub zog loj zuj zus uas ua rau cov ntshav qabzib-insulin muaj peev xwm ua rau muaj cov ntshav qabzib ntau yam thiab muaj lwm yam teebmeem ntshav qabzib ntau ntxiv rau cov neeg mob ntshav qab zib hom 2.

Cov amino acid sib lawv liag ntawm exenatide ib nrab sib raug rau ntu ntawm tib neeg GLP-1, los ntawm qhov uas nws khi thiab ua rau GLP-1 cov neeg txais kev pabcuam hauv tib neeg, uas ua rau muaj kev nce siab ntau dua cov ntshav qabzib thiab kev tso ntshav ntawm insulin los ntawm pancreatic cells-hlwb nrog kev koom tes ntawm cyclic AMP thiab / lossis lwm yam kev cuam tshuam ntawm cov ntshav. txoj kev. Exenatide txhawb kev tso tawm ntawm insulin los ntawm β-hlwb lub xub ntiag ntawm cov ntshav siab ntau.

Exenatide sib txawv hauv cov qauv tshuaj thiab cov tshuaj pharmacological los ntawm insulin, sulfonylurea derivatives, D-phenylalanine derivatives thiab meglitinides, biguanides, thiazolidinediones thiab alpha-glucosidase inhibitors.

Exenatide txhim kho glycemic tswj nyob rau hauv cov neeg mob uas muaj ntshav qab zib hom 2 vim yog cov haujlwm hauv qab no.

Hauv hyperglycemic tej yam kev mob, exenatide ua rau cov piam thaj tsis muaj peev xwm tso cov kua dej los ntawm cov tshuaj tua kabmob (pancreatic cells-cells). Qhov insulin secretion tso tseg thaum cov concentration ntawm cov piam thaj hauv cov ntshav txo qis thiab nws nce mus rau qhov qub, yog li txo cov kev pheej hmoo ntawm cov ntshav qog ntshav qab zib.

Cov tshuaj insulin zais hauv thawj 10 feeb (hauv kev teb rau kev muaj glycemia ntau dua), hu ua "thawj theem ntawm cov tshuaj insulin", tshwj xeeb tshaj yog tsis tuaj rau cov neeg mob ntshav qab zib hom 2. Tsis tas li ntawd, qhov poob ntawm thawj theem ntawm cov tshuaj insulin yog ib qho kev ua haujlwm thaum ntxov ntawm function-cell ua haujlwm ntawm hom ntshav qab zib 2. Kev tswj hwm ntawm exenatide rov qab los yog hloov kho tau zoo ntau theem ntawm thawj thiab theem ob ntawm cov tshuaj insulin hauv cov neeg mob uas muaj ntshav qab zib hom 2.

Hauv cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus tawm tsam keeb kwm ntawm hyperglycemia, kev coj noj coj ua ntawm exenatide txwv kev tso cia ntau dhau ntawm glucagon. Txawm li cas los xij, exenatide tsis cuam tshuam rau lub cev glucagon teb li cas rau kev mob ntshav qab zib.

Nws tau pom tias kev coj noj coj ua ntawm exenatide ua rau kev poob qis thiab ua kom tsawg dua ntawm txoj kev noj zaub mov, inhibits lub cev muaj zog ntawm lub plab, uas ua rau lub qeeb ntawm nws qhov khoob.

Hauv cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus, kev kho mob exenatide ua ke nrog metformin, thiazolidinedione thiab / los yog sulfonylurea kev npaj ua rau txo qis rau cov ntshav qabzib, ntshav qabzib tom qab, nrog rau HbA 1c, yog li txhim kho glycemic tswj hauv cov neeg mob no.

Tom qab s / c tswj hwm ntawm exenatide ntawm ib koob ntawm 10 μg rau cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus, exenatide nrawm nrawm thiab nce mus txog nruab nrab C max tom qab 2.1 teev, uas yog 211 pg / ml, AUC o-inf yog 1036 pg × h / ml. Thaum tso tawm rau exenatide, AUC nce rau hauv kev faib ua feem rau cov koob tshuaj nce ntxiv los ntawm 5 μg txog 10 μg, thaum tsis muaj qhov sib npaug ntawm C max. Tib cov txiaj ntsig tau pom nrog kev coj ua subcutaneous ntawm exenatide hauv plab, ncej puab lossis caj npab.

V d ntawm exenatide tom qab sc tswj hwm yog 28.3 L.

Kev ntsuas phoo thiab nthuav tawm

Exenatide yog feem ntau raug ntog los ntawm glomerular pom ua raws los ntawm kev kho mob proteolytic kev ua haujlwm. Exenatide tshem tawm yog 9.1 l / h. Qhov kawg T 1/2 yog 2.4 teev. Cov tshuaj pharmacokinetic ntawm exenatide yog koob tshuaj ywj siab. Ntsuas qhov ntau ntawm exenatide raug txiav txim kwv yees li 10 teev tom qab noj tshuaj.

Pharmacokinetics hauv cov chaw kuaj mob tshwj xeeb

Hauv cov neeg mob uas muaj mob me me los yog mob raum (CC 30-80 ml / min), kev tshem tawm tsis yog qhov txawv ntawm kev ua kom pom tseeb hauv cov neeg mob uas lub raum tsis ua haujlwm, yog li ntawd, kev kho tshuaj tsis tas yuav tsum tau. Txawm li cas los xij, hauv cov neeg mob uas mob raum ua rau lub raum tsis ua haujlwm, kev txiav txim siab nruab nrab yog txo mus rau 0.9 l / h (piv rau 9.1 l / teev hauv cov ntsiab lus noj qab haus huv).

Txij li thaum exenatide feem ntau yog ua rau lub raum, nws ntseeg tau tias kev ua haujlwm hauv daim siab ua haujlwm tsis hloov pauv qhov tshwj xeeb ntawm exenatide hauv cov ntshav.

Lub hnub nyoog tsis cuam tshuam rau pharmacokinetic cov yam ntxwv ntawm exenatide. Yog li, cov neeg laus laus tsis tas yuav tsum ua qhov hloov kho koob tshuaj.

Cov pharmacokinetics ntawm exenatide hauv cov menyuam hnub nyoog qis dua 12 xyoos tsis tau kawm.

Hauv kev kawm pharmacokinetic nyob rau cov tub ntxhais hluas hnub nyoog 12 txog 16 xyoo nrog hom 2 mob ntshav qab zib mellitus, thaum exenatide tau raug tshaj tawm ntawm koob tshuaj 5 μg, pharmacokinetic tsis zoo ib yam li cov neeg laus.

Tsis muaj qhov sib txawv ntau qhov sib txawv ntawm tus txiv neej thiab poj niam hauv pharmacokinetics ntawm exenatide.

Cov chaw muag tshuaj ntawm exenatide hauv cov neeg sawv cev ntawm ntau haiv neeg sib txawv tsis hloov. Tsis tas yuav muab hloov kho los ntawm haiv neeg keeb kwm.

Tsis muaj qhov tshwm sim pom tseeb ntawm kev ntsuas lub cev (BMI) thiab exenatide pharmacokinetics. Koob tshuaj hloov kho raws li BMI yog tsis xav tau.

Kev Qhia Tawm BAETA

Cov ntaub ntawv los ntawm BAETA pab:

- Hom 2 mob ntshav qab zib mellitus raws li kev kho mob monotherapy ntxiv rau kev noj haus thiab kev tawm dag zog kom ua tiav kev tswj glycemic.

- hom 2 mob ntshav qab zib mellitus ua kev kho mob ntxiv rau metformin, sulfonylurea derivative, thiazolidinedione, kev sib xyaw ntawm metformin thiab sulfonylurea derivative, lossis metformin thiab thiazoldinedione yog tias tswj tau glycemic tsis tiav.

Sab sij huam ntawm BAETA

Cov kev tshwm sim tsis zoo uas tshwm sim ntau dua li ntawm qhov teeb meem raug cais tawm tau teev raws li cov ntawv pov thawj hauv qab: feem ntau (≥10%), feem ntau (≥1%, tab sis Cov kev tawm tsam hauv zos: ntau zaus - khaus ntawm qhov chaw txhaj tshuaj, tsis tshua muaj - tawm pob, ua pob liab liab hauv chaw txhaj tshuaj.

Los ntawm lub plab zom mov: feem ntau - xeev siab, ntuav, raws plab, dyspepsia, ploj plab.

Los ntawm ib sab ntawm lub hauv nruab nrab lub paj hlwb: feem ntau - kiv taub hau.

Thaum siv Bayeta ® raws li kev kho mob monotherapy, qhov tshwm sim ntawm kev mob ntshav qab zib yog 5% piv nrog 1% cov placebo.

Feem ntau qhov tshwm sim ntawm hypoglycemia hauv kev sib zog tau mob me lossis mob pesnrab.

Cov kev phiv tshuaj uas tshwm sim ntau tshaj li qhov tsis xws li raug teev tseg raws li cov kev paub hauv qab no: feem ntau (≥10%), feem ntau (≥1%, tab sis los ntawm cov txheej txheem hauv plab: feem ntau heev - xeev siab, ntuav, raws plab, feem ntau - txo qab los noj mov, dyspepsia, mob plab zom mov, tsis txaus ntseeg - mob plab, tsam plab, duav, cem quav, saj ntxhias, pom kev tsis txaus, tsis tshua muaj tus mob txhawm rau mob. tsis-ua si.

Los ntawm sab hauv nruab nrab ntawm lub hauv nruab nrab lub paj hlwb: feem ntau - kiv taub hau, mob taub hau, tsis tshua muaj - tsaug zog.

Los ntawm cov kab mob endocrine: feem ntau - hypoglycemia (hauv kev sib xyaw nrog sulfonylurea derivative). Vim hais tias qhov zaus ntawm hypoglycemia nce nrog kev siv qhov tseeb ntawm Bayeta ® nrog sulfonylurea derivatives, nws yog qhov tsim nyog los muab rau txo qis ntawm cov tshuaj sulfonylurea derivatives nrog kev pheej hmoo ntawm hypoglycemia. Feem ntau qhov tshwm sim ntawm lub qog ntshav qab zib hauv kev sib zog tau mob me me lossis mob nyhav, thiab tau tso tseg los ntawm kev noj zaub mov carbohydrates.

Los ntawm sab hauv cov metabolism: feem ntau - hyperhidrosis, tsis tshua muaj - lub cev qhuav dej (cuam tshuam nrog xeev siab, ntuav thiab / lossis raws plab).

Los ntawm cov kab mob urinary: tsis tshua muaj - hnov ​​mob raum muaj nuj nqi, suav nrog mob raum tsis ua hauj lwm, exacerbation ntawm chav kawm ntawm kev mob raum tsis ua hauj lwm, cov ntshiab si creatinine.

Kev ua xua: tsis tshua muaj - angioedema, tsis tshua muaj tshwm sim - anaphylactic kev hloov.

Cov tshuaj tiv thaiv hauv zos: feem ntau - khaus ntawm qhov chaw txhaj tshuaj, tsis tshua muaj pob - liab, liab ntawm thaj chaw txhaj tshuaj.

Lwm yam: feem ntau - pauv, tsis muaj zog.

Ntau qhov xwm txheej ntawm lub sijhawm coagulation ntau dua tau tshaj tawm nrog kev siv warfarin thiab exenatide tib lub sijhawm, uas tsis tshua muaj los nrog los ntshav.

Feem ntau, cov kev mob tshwm sim tau mob sib khuav me me los sis mob hnyav thiab tsis ua rau txo kev kho mob.

Tshaj Lij (kev tshaj tawm tom qab) xov

Kev ua xua rau: muaj tsawg kawg - kev phiv tshuaj tiv thaiv.

Kev tsis sib haum xeeb ntawm kev noj zaub mov thiab cov metabolism: tsis tshua muaj lub cev - lub cev qhuav dej, feem ntau cuam tshuam nrog xeev siab, ntuav thiab / lossis zawv plab, poob phaus.

Los ntawm cov kab mob hauv lub cev: dysgeusia, tsaug zog.

Los ntawm cov txheej txheem hauv plab: belching, cem quav, flatulence, tsis tshua muaj tshwm sim - mob ncauj mob leeg.

Los ntawm cov kab mob txeeb zis: hloov pauv lub raum kev ua haujlwm, incl. mob raum tsis ua hauj lwm, exacerbation ntawm mob raum tsis ua hauj lwm, lub raum khiav tsis zoo, nce ntshav muaj zog zuj zus.

Dermatological tshua: maculopapular tawm pob, khaus tawv nqaij, urticaria, angioedema, alopecia.

Kev tshawb nrhiav hauv chav kuaj: ib qho kev nce ntxiv hauv INR (thaum muab tshuaj nrog warfarin), hauv qee kis muaj feem cuam tshuam nrog kev txhim kho los ntshav.

Yog tias muaj kev noj ntau dhau (noj 10 zaug qhov koob pom zoo tshaj plaws), cov tsos mob hauv qab no tau pom tias: xeev siab thiab ntuav, nrog rau kev txhim kho ntshav qab zib sai sai.

Kev Kho Mob: Kev kho mob yam mob yog ua tiav, suav nrog kev tswj hwm hauv lub cev ntawm cov ntshav qabzib yog tias mob ntshav nce siab ntau.

Bayeta ® yuav tsum siv nrog ceev faj hauv cov neeg mob noj lub qhov ncauj npaj yuav tsum nqus sai los ntawm kev mob plab, uas yog Baeta ® yuav ncua kev mob plab zom mov. Cov neeg mob yuav tsum raug qhia kom noj cov tshuaj hauv qhov ncauj, cov nyhuv ntawm nws nyob ntawm lawv lub luag haujlwm tseem ceeb (piv txwv, tshuaj tua kab mob), tsawg kawg 1 teev ua ntej kev tswj hwm ntawm exenatide. Yog tias cov tshuaj no yuav tsum tau noj nrog zaub mov, tom qab ntawd lawv yuav tsum noj thaum cov zaub mov noj thaum cov tshuaj exenatide tsis tau txais.

Nrog kev tswj hwm tib lub sijhawm ntawm digoxin (0.25 mg 1 lub sijhawm / hnub) nrog Baeta ® kev npaj, C max ntawm digoxin txo qis li 17%, thiab T max nce li 2.5 teev. Txawm li cas los xij, AUC hauv lub xeev qhov sib npaug tsis hloov.

Nrog cov lus qhia ntawm Bayeta ®, AUC thiab C max ntawm lovastatin txo los ntawm kwv yees li 40% thiab 28%, feem, thiab T max nce kwv yees li 4 teev. Kev sib koom tes ntawm Bayeta ® nrog HMG-CoA reductase inhibitors tsis nrog kev hloov pauv hauv ntshav lipid muaj pes tsawg leeg (HDL) -cov roj cholesterol, LDL cov roj (cholesterol), tag nrho cov roj (cholesterol) thiab TG).

Hauv cov neeg mob uas muaj ntshav me los sis mob ntshav liab, nyob ruaj khov thaum noj lisinopril (5-20 mg / hnub), Bayeta ® tsis hloov pauv ntawm AUC thiab C max ntawm lisinopril ntawm kev sib npaug. T max ntawm lisinopril ntawm qhov sib luag ntawm cov xuab moos tau nce li 2 teev .Txawm tsis muaj kev hloov pauv hauv nruab nrab txhua hnub systolic thiab diastolic cov ntshav siab.

Nws tau sau tseg tias nrog kev qhia txog warfarin 30 feeb tom qab kev npaj Baeta max T max nce li 2 teev. Kev kho mob tseem ceeb hauv C max thiab AUC tsis pom.

Kev siv Bayeta ® nrog cov tshuaj insulin, tshuaj ntsuab ntawm D-phenylalanine, meglitinide lossis alpha-glucosidase inhibitors tsis tau kawm.

Tsis txhob noj cov tshuaj tom qab noj mov. Nws tsis pom zoo hauv / hauv lossis hauv / m tswj hwm ntawm cov tshuaj.

Bayeta ® yuav tsum tsis txhob siv yog tias pom muaj nyob hauv qhov kev daws teeb meem lossis yog hais tias daws tau pos huab lossis muaj xim.

Vim tias lub peev xwm tiv thaiv kab mob ntawm cov tshuaj uas muaj cov protein thiab peptides, kev txhim kho ntawm cov tshuaj tiv thaiv rau exenatide yog ua tau thaum kho nrog Bayeta ®. Hauv feem ntau ntawm cov neeg mob hauv kev ua cov tshuaj tiv thaiv kab mob tau sau tseg, lawv cov titer txo qis raws li kev kho mob txuas ntxiv thiab tseem qis rau 82 lub lis piam. Lub xub ntiag ntawm cov tshuaj tiv thaiv tsis cuam tshuam qhov zaus thiab hom ntawm cov kev mob tshwm sim.

Cov neeg mob yuav tsum tau paub tias kev kho mob nrog Bayeta ® tuaj yeem ua rau tsis qab los noj mov thiab / lossis lub cev hnyav, thiab tias vim muaj cov teebmeem no tsis tas yuav hloov pauv kev noj tshuaj.

Hauv kev tshawb fawb preclinical hauv cov nas thiab nas, tsis muaj cov teebmeem carcinogenic ntawm exenatide pom. Thaum ib koob tshuaj tau siv nyob rau hauv cov nas uas yog 128 lub sij hawm koob tshuaj hauv tib neeg, ntau tus lej hauv C-cell cov thyroid adenomas tau sau tseg tsis muaj cov cim tsis zoo, uas cuam tshuam nrog kev nce hauv lub neej ntawm kev sim cov tsiaj uas tau txais exenatide.

Cov mob raum tsis zoo ntawm lub raum kev ua haujlwm tau raug tshaj tawm, suav nrog kev nce ntxiv ntawm cov ntshav dej, kev txhim kho lub raum ua kom tsis zoo, ua rau lub siab mob mus rau lub raum thiab mob raum tsis ua haujlwm, thiab qee zaum hemodialysis xav tau. Qee qhov tshwm sim no tau pom nyob rau hauv cov neeg mob uas tau txais ib lossis ntau dua cov tshuaj pharmacological uas cuam tshuam rau lub raum kev ua haujlwm / dej metabolism thiab / lossis tawm tsam lwm cov xwm txheej tsis zoo uas ua rau lub cev tsis muaj zog, xws li xeev siab, ntuav thiab / lossis raws plab. Cov tshuaj tsis haum xeeb suav nrog ACE inhibitors, NSAIDs, thiab diuretics. Thaum sau tshuaj kho cov tsos mob thiab kev txiav tsis ua yeeb tshuaj, txawm tias yog vim li cas ntawm kev hloov pauv pathological, kev ua haujlwm tsis zoo hauv lub raum tau rov qab los. Thaum ua qhov kev npaj ua ntej thiab kev tshawb fawb ntawm exenatide, cov pov thawj ntawm cov nephrotoxicity ncaj tsis pom.

Tsis tshua muaj neeg qhia txog kev mob voos nyias ua paug thaum siv Bayeta ®. Cov neeg mob yuav tsum tau qhia paub txog cov yam ntxwv ntawm tus yam ntxwv ntawm tus mob pancreatitis: mob hnyav plab heev. Thaum kws kho mob muab tshuaj tua kab mob, kev daws teeb meem ntawm tus mob pancreatitis zoo.

Cov neeg mob ua ntej pib kev kho mob nrog Bayeta ® yuav tsum paub lawv tus kheej nrog phau ntawv qhia rau kev siv rab koob xaum xim uas txuas nrog rau cov tshuaj.

Sau npe B. Cov tshuaj yuav tsum khaws cia ntawm qhov kub ntawm 2 ° txog 8 ° C. Txee lub neej yog 2 xyoos.

Ib qho yeeb tshuaj uas siv hauv cov kua hauv lub tes yuav tsum muab cia rau qhov kub tsis tshaj 25 ° C rau tsis pub dhau 30 hnub.

Cov tshuaj yuav tsum khaws cia kom ncav tsis cuag cov menyuam yaus, tiv thaiv los ntawm kev nphav raug rau lub teeb, tsis txhob ua kom khov.