Kev Siv Tshuaj Yeeb: cov lus qhia rau kev siv > Kev khomob thiab kev tiv thaiv

Daim ntawv txiav txim - kev daws teeb meem rau kev tswj hwm subcutaneous: tsis muaj xim lossis yuav luag tsis muaj xim (3 ml txhua * hauv cov ntawv ntim iav, uas tau muab ntim rau hauv cov hnab yas xau pov tseg rau ntau qhov kev txhaj tshuaj, hauv ib pob duab los ntawm 1, 2 lossis 3 koob txhaj tshuaj).

* Hauv 1 rab koob xaum (3 ml) muaj 10 koob tshuaj 1.8 mg, 15 koob ntawm 1.2 mg lossis 30 koob ntawm 0.6 mg.

Cov tshuaj tseem ceeb: liraglutide, hauv 1 ml - 6 mg.

Ntu cov khoom siv: hydrochloric acid / sodium hydroxide q.s., sodium hydrogen phosphate dihydrate, phenol, propylene glycol, dej rau kev txhaj tshuaj.

Cov yam ntxwv Pharmacological:

Cov Tshuaj Hauv Tshuaj
Liraglutide muaj cov kev pab cuam ntev li 24 teev thiab txhim kho glycemic tswj los ntawm kev txo qis cov concentration ntawm cov roj ntsha sai thiab tom qab noj mov hauv cov neeg mob uas muaj ntshav qab zib hom 2.
Cov kua nplaum-cov kua nyeem cov kua dej muaj cov kua qab
Nrog kev nce ntxiv hauv cov ntshav qabzib concentration, liraglutide ntau ntxiv insulin secretion. Thaum siv stepwise qab zib infusion, insulin secretion tom qab tswj hwm ntawm ib koob ntawm liraglutide rau cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus nce rau hauv qib piv rau cov uas muaj kev noj qab haus huv (Daim 1).

Pancreatic beta ntawm tes ua haujlwm
Liraglutide txhim kho pancreatic beta cell muaj nuj nqi, raws li muaj pov thawj los ntawm thawj ntu thiab theem ob ntawm cov tshuaj insulin thiab qhov kev ua haujlwm siab kawg ntawm beta hlwb. Pharmacodynamic cov kev tshawb fawb ntawm cov neeg mob uas muaj ntshav qab zib hom 2 tau qhia txog kev rov qab los ntawm thawj theem ntawm insulin secretion (kev tswj hwm ntawm insulin), kev txhim kho ntawm theem ob ntawm insulin secretion (hyperglycemic clamp test) thiab qhov siab tshaj plaws zais cia kev ua haujlwm ntawm insulin (arginine stimulation test).
Lub sijhawm 52-lub lim tiam kho nrog Victoza ®, muaj kev txhim kho hauv kev ua haujlwm ntawm pancreatic beta hlwb, raws li muaj pov thawj los ntawm kev ntsuam xyuas cov qauv homeostatic ntawm kev ua haujlwm ntawm pancreatic beta hlwb (HOMA index) thiab qhov piv ntawm insulin rau proinsulin.
Glucagon tso pa tawm:
Liraglutide, txhawb kev tawm tsam cov kua dej ntawm cov tshuaj insulin thiab inhibiting qhov zais cia ntawm glucagon, txo qhov concentration ntawm cov piam thaj hauv cov ntshav. Liraglutide tsis inhibit glucagon teb rau cov ntshav qabzib feem ntau. Tsis tas li ntawd, tawm tsam cov keeb kwm ntawm liraglutide, qis dua cov dej qabzib endogenous tau pom.
Phaj plab muab nchuav:
Liraglutide ua rau qeeb me ntsis ntawm lub plab zom mov, yog li txo qhov kev siv ntawm postprandial qabzib rau hauv cov ntshav.
Lub cev nyhav, lub cev sib xyaw thiab kev siv lub zog:
Hauv cov ncauj lus nrog kev hnyav lub cev nyob nrog rau kev tshawb nrhiav mus sij hawm ntev ntawm cov kab mob liraglutide, tom kawg ua rau lub cev hnyav dua li qhov hnyav. Kev soj ntsuam uas siv kev suav tomography (CT) thiab lub zog hluav taws xob X-ray absorptiometry (DERA) cov kev qhia tau hais tias qhov poob ntawm lub cev qhov hnyav tau tshwm sim feem ntau vim ploj ntawm cov neeg mob adipose cov ntaub so ntswg. Cov txiaj ntsig tau piav qhia los ntawm qhov tseeb tias thaum lub sij hawm kho nrog liraglutide hauv cov neeg mob, kev tshaib plab thiab lub zog siv tsawg.
Electrophysiology ntawm lub plawv (Efc):
Cov nyhuv ntawm liraglutide ntawm cov txheej txheem ntawm rov kho dua hauv lub plawv tau sim hauv kev tshawb fawb ntawm EFS. Kev siv cov liraglutide nyob rau hauv kev sib xyaw ua ke nyob rau hauv ib koob tshuaj txhua hnub txog li 1.8 mg tsis tsim tawm ntev ntawm EPS.
Cov chaw kho mob ua tau
3992 cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus tau nyob rau hauv 5 lub qhov muag pom ob qho kev kuaj mob ntawm kev nyab xeeb thiab kev ua tau zoo los ntsuas qhov cuam tshuam ntawm Victoza ® ntawm glycemic tswj. Victoza ® txoj kev kho tau tsim cov chaw kho mob thiab cov ntawv txhim kho hauv HbA_1syoo qabzib thiab qabzib cov qabzib feem ntau piv nrog cov placebo.
Glycemic tswj
Cov tshuaj Viktoza ® nyob rau hauv daim ntawv ntawm monotherapy rau 52 lub lis piam ua rau muaj kev txheeb cais (p ®, thaum nyob rau hauv cov neeg mob koom nrog kev soj ntsuam ntawm kev sib xyaw ntawm kev siv tshuaj yeeb tshuaj Victoza ®, nruab nrab HbA_1s txo los ntawm 1.1-2.5%.
Cov tshuaj Viktoza ® thaum 26-lub lim tiam ua ke nrog kev kho mob nrog metformin, sulfonylurea kev npaj lossis metformin thiab thiazolidinedione ua rau muaj kev mob siab (p ® thiab metformin, qhov sib ntxiv ntawm insulin detemir muab ntau dua kev ua haujlwm piv nrog cov tshuaj Victoza ® thiab metformin tom qab 26 lub lis piam ntawm kev kho mob (txo qis HbA1c los ntawm 0.52%).
Nws tau muaj pov thawj tias qhov ua tau zoo ntawm cov tshuaj Victoza ® hauv ib koob ntawm 0.6 mg nyob rau hauv kev sib xyaw nrog sulfonylurea lossis metformin kev npaj tau zoo dua rau cov placebo, tab sis tib lub sijhawm tsawg dua li ntawm 1,2 mg thiab 1.8 mg.
Qhov feem ntawm cov neeg mob uas ua tiav HbA txo qis_1s
Tawm tsam keeb kwm yav dhau los ntawm kev kho mob monotherapy nrog Viktoza ® lub sijhawm tshawb fawb 52-lub lim tiam, tus naj npawb ntawm cov neeg mob uas ua tiav HbA_1s ® kev sib xyaw nrog metformin, sulfonylurea derivatives, lossis kev sib xyaw ntawm metformin thiab thiazolidinedione, tus naj npawb ntawm cov neeg mob uas tau mus txog HbA_1s ≤ 6.5%, cov ntsiab lus tseem ceeb (p ≤ 0.0001) nce ntxiv txog kev muaj mob ntawm cov neeg mob uas tau txais kev kho mob ib leeg, tsis tas li ntawm Victoza ®, nrog cov tshuaj hypoglycemic.
Hauv cov pab pawg ntawm cov neeg mob uas tsis ua tiav glycemic tswj lub sijhawm kho nrog Victoza met thiab metformin, feem pua ntawm cov neeg mob uas ua tiav HbA._1s (B HbA tiav_1s ® ob qho tib si rau hauv kev kho mob, thiab muaj kev sib xyaw nrog ib lossis ob qhov ncauj tshuaj hypoglycemic. Qhov kev txo qis no tau pom twb muaj nyob hauv thawj ob lub lis piam los ntawm kev pib kho.
Postprandial Glycemia
Kev siv cov tshuaj Victoza ® rau peb hnub ntawm kev noj cov zaub mov tseem ceeb tau pab txo qis kev sib txuam ntawm cov piam thaj tom qab ntawm 31-49 mg% (1.68-2.71 mmol / l).
Lub cev hnyav
52 lub lis piam monotherapy nrog Viktoza ® tau cuam tshuam nrog txhawb kev poob phaus.
Thoob plaws lub sijhawm tag nrho ntawm cov chaw soj ntsuam, kev txhawb nqa kev poob phaus kuj tau cuam tshuam txog kev siv Victoza ® ua ke nrog metformin thiab kev sib xyaw nrog metformin thiab sulfonylureas lossis kev sib xyaw ntawm metformin thiab thiazolidinedione.
Kev hnyav dua hauv cov neeg mob uas tau txais Victoza ® nrog metformin kuj tau pom tom qab ntxiv ntawm insulin detemir.
Qhov kev poob hnyav tshaj plaws hauv lub cev tau pom nyob rau hauv cov neeg mob uas muaj qhov nruab nrab ntawm lub cev qhov hnyav (BMI) thaum pib ntawm txoj kev tshawb no.
Kev kho mob monotherapy nrog Viktoza ® rau 52 lub lis piam ua rau qhov txo qis hauv nruab nrab lub duav ntawm 3.0-3.6 cm.
Txo qhov hnyav hauv lub cev tau raug soj ntsuam nyob rau hauv txhua tus neeg mob tau txais kev kho mob nrog Victoza ®, tsis hais seb puas muaj kev cuam tshuam tsis zoo nyob rau hauv daim ntawv ntawm xeev siab.
Cov tshuaj Viktoza ® ua ib feem ntawm kev sib xyaw ua ke nrog metformin txo qhov ntim ntawm subcutaneous rog li ntawm 13-17%.
Tsis yog cawv cawv steatohepatosis
Liraglutide txo qhov hnyav ntawm steatohepatosis hauv cov neeg mob ntshav qab zib hom 2.
Ua ntshav siab
Kev tshawb nrhiav mus sij hawm ntev tau pom tias cov tshuaj Victoza ® txo cov ntshav systolic los ntawm qhov nruab nrab li ntawm 2.3-6.7 hli Hg. hauv thawj ob lub lim tiam ntawm kev kho mob. Kev poob qis hauv cov ntshav systolic tau tshwm sim ua ntej pib yuag poob.
Lwm cov ntaub ntawv soj ntsuam
Hauv kev sib piv kev kawm txog qhov ua tau zoo thiab kev nyab xeeb ntawm cov tshuaj Victoza ® (ntawm koob tshuaj ntawm 1,2 mg thiab 1.8 mg) thiab qhov inhibitor ntawm dipeptidyl peptidase-4 sitagliptin ntawm koob tshuaj 100 mg rau cov neeg mob uas tsis ua tiav kev tswj hwm ntawm kev siv tshuaj metformin, qhov zoo tshaj plaws tau pov thawj tom qab 26 lub lim tiam ntawm kev kho mob HbA_1s thaum siv tshuaj yaj yeeb Victoza ® hauv ob qho tshuaj txhaj piv rau sitagliptin (-1.24%, -1.50% piv rau -0.90%, p ® piv rau sitagliptin (43.7% thiab 56.0% los ntawm piv nrog 22.0%, p ® tau nce siab dua piv nrog cov neeg mob tau txais sitagliptin (-2.9 kg thiab -3.4 kg, piv nrog -1.0 kg, p ®, xeev siab) muaj ntau dua. xeev siab tsis muaj puv sij hawm, thiab qhov tshwm sim ntawm cov ntshav qog ua kom tsawg tsis txawv ntau thaum kho nrog Victoza ® thiab sitagliptin (0.178 thiab 0.161, piv nrog 0.106 mob / neeg mob ib xyoos)._1s thiab qhov zoo ntawm Viktoza ® piv rau sitagliptin tau pom tom qab 26th lub lim tiam ntawm kev kho mob nrog Viktoza ® (1.2 mg thiab 1.8 mg) thiab tau lees paub tom qab 52 lub lis piam ntawm kev kho mob (-1.29% thiab -1.51%) piv nrog -0.88%, p ®, uas ua rau muaj kev txo qis ntxiv thiab cov lus pom zoo hauv HbA_1s nyob rau ntawm 78 lub lim tiam ntawm kev kho mob (0.24% thiab 0.45%, 95 Cl: txij li 0.41 txog 0.07 thiab txij -0.67 txog 0.23).
Hauv kev sib piv kawm txog qhov ua tau zoo thiab kev nyab xeeb ntawm cov tshuaj Victoza ® (ntawm koob tshuaj 1.8 mg) thiab exenatide (ntawm koob tshuaj 10 μg ob zaug hauv ib hnub) hauv cov neeg mob uas tsis ua tiav kev tswj txaus rau kev kho nrog metformin thiab / lossis sulfonylurea derivatives, tom qab 26 lub lis piam ntawm kev siv tshuaj Lub Vev xaij Victoza ® pom tias qhov qis dua hauv HbA_1s piv nrog exenatide (-1.12% piv nrog -0.79%, p ® piv nrog exenatide (54.2% piv nrog 43.4%, p = 0.0015). Cov kev kho ob leeg qhia pom nruab nrab poob lub cev qhov hnyav ntawm kwv yees li 3 kg. Tus naj npawb ntawm cov neeg mob qhia tias xeev siab yog qis dua nyob rau hauv pab pawg ntawm cov neeg mob tau txais tshuaj Viktoza ®, piv nrog exenatide. Qhov xwm txheej ntawm cov ntshav qog ntshav qab zib tsawg dua nyob rau hauv pab pawg ntawm cov neeg mob tau txais tshuaj Viktoza ®, piv nrog exenatide ( 1 932 piv nrog 2 600 tus neeg mob / tus neeg mob ib xyoos, p = 0.01). Tom qab 26 lub lim tiam ntawm kev tswj hwm exenatide, cov neeg mob yuav tau pauv mus rau Victoza ®, uas ua rau txo qis ntxiv hauv HbA_1s ntawm 40 lub lim tiam ntawm kev kho mob (-0.32%, p ® rau 52 lub lis piam txhim kho cov tshuaj insulin rhiab heev dua piv rau cov sulfonylurea npaj, uas tau qhia siv cov qauv hauv tsev rau kev soj ntsuam HOMA-IR insulin tsis kam.

Cov Tshuaj Pharmacokinetics
Kev Tsis Txaus Siab
Qhov nqus ntawm liraglutide tom qab subcutaneous kev tswj hwm yog qeeb, lub sijhawm nce mus txog qhov siab tshaj plaws ntshav plasma yog 8-12 teev tom qab koob tshuaj. Kev siab tshaj plaws (C_max) liraglutide nyob rau hauv cov ntshav tom qab subcutaneous txhaj tshuaj hauv ib koob ntawm 0.6 mg yog 9.4 nmol / L. Nrog kev qhia txog liraglutide ntawm kev noj tshuaj ntawm 1.8 mg, qhov ntsuas nruab nrab ntawm nws qhov sib luag ntawm cov ntshav plasma concentration (AUC)_?/24) nce mus txog kwv yees li 34 nmol / L. Cov kis ntawm liraglutide yog ua kom zoo dua nyob rau hauv kev faib ua feem rau cov koob tshuaj tau muab. Tom qab tswj hwm ntawm liraglutide nyob rau hauv ib qho tshuaj xwb, cov kab mob intrapopulation coefficient ntawm qhov sib txawv ntawm thaj chaw hauv qab qhov ntsuas-sijhawm nkhaus ntawm AUC yog 11%. Qhov tseeb ntawm bioavailability ntawm liraglutide tom qab kev tswj hwm subcutaneous yog kwv yees li 55%.
Kev xa Khoom
Cov pom meej ntim ntawm kev faib tawm ntawm liraglutide hauv cov ntaub so ntswg tom qab kev tswj hwm subcutaneous yog 11-17 litres. Qhov nruab nrab ntim ntawm kev faib tawm ntawm liraglutide tom qab kev tswj hwm dej khov yog 0.07 l / kg. Liraglutide ntau khi rau cov ntshav plasma (> 98%).
Kev zom zaub mov
Txog 24 teev tom qab saib xyuas kev noj qab haus huv rau cov neeg tuaj yeem noj qab nyob zoo ntawm ib qho koob tshuaj 3 H-liraglutide sau npe nrog lub xov tooj cua isotope, lub ntsiab plasma tseem tsis hloov pauv liraglutide. Tau kuaj pom ob lub plasma ntshav dawb (≤ 9% thiab ≤ 5% ntawm tag nrho cov ntshav ntshav ntshav). Liraglutide yog metabolized endogenously, zoo li cov protein loj, tsis muaj feem nrog ib qho hloov khoom nruab nrog raws li txoj kev tso tawm.
Chaw Sau Ntawv
Tom qab tau noj 3 H-liraglutide siv, tshuaj liraglutide tsis hloov pauv tsis pom nyob rau hauv cov zis lossis quav. Tsuas yog ib feem me me ntawm kev tswj hwm radioactivity hauv daim ntawv ntawm metabolites cuam tshuam nrog liraglutide (6% thiab 5%, feem) tau raug cais tawm los ntawm lub raum lossis dhau los ntawm cov hnyuv. Cov tshuaj kua hluav taws xob raug tawm ntawm lub raum los yog los ntawm txoj hnyuv, feem ntau yog nyob rau thawj 6-8 hnub tom qab cov tshuaj, thiab yog peb yam tshuaj lom. Qhov kev txiav txim siab nruab nrab ntawm lub cev tom qab tswj hwm ntawm liraglutide nyob rau hauv ib koob tshuaj yog kwv yees li 1.2 l / h nrog kev tshem tawm ib nrab-lub neej ntawm kwv yees li 13 teev.
Cov pab pawg neeg tshwj xeeb
Hnub nyoog laus: Pharmacokinetic cov kev tshawb fawb hauv ib pawg neeg noj qab nyob zoo thiab tsom xam cov ntaub ntawv pharmacokinetic tau nyob hauv cov neeg mob (hnub nyoog 18 txog 80 xyoo) qhia tias lub hnub nyoog tsis muaj kev cuam tshuam loj hauv lub pharmacokinetic khoom ntawm liraglutide.
Tub los ntxhais: Kev soj ntsuam ntawm cov pejxeem-cov kws kho mob ntawm cov ntaub ntawv tau los ntawm kev kawm txog cov teebmeem ntawm liraglutide hauv cov pojniam thiab tus txiv neej cov neeg mob, thiab kev tshawb fawb pharmacokinetic nyob rau hauv ib pawg neeg noj qab haus huv qhia tau tias tus tub lossis ntxhais tsis muaj kev cuam tshuam loj hauv lub pharmacokinetic khoom ntawm liraglutide.
Haiv neeg: Ib tug pej xeem-based pharmacokinetic tsom xam ntawm cov ntaub ntawv tau txais hauv kev kawm txog kev cuam tshuam ntawm liraglutide nyob rau hauv kev kawm ntawm cov neeg tawv dawb, dub, Neeg Esxias thiab Latin Asmeskas cov haiv neeg qhia tias haiv neeg tsis muaj kev cuam tshuam loj hauv lub pharmacokinetic khoom ntawm liraglutide.
Kev pham: Ib tug pej xeem-based pharmacokinetic tsom xam ntawm cov ntaub ntawv qhia tias lub cev lub cev qhov ntsuas (BMI) tsis muaj kev cuam tshuam loj hauv kev kho mob rau cov khoom lag luam pharmacokinetic ntawm liraglutide.
Mob siab:
Cov chaw muag tshuaj ntawm cov tshuaj liraglutide tau tshawb fawb txog kev tshawb fawb txog ib zaug ntawm cov tshuaj hauv cov kws muaj ntau qib tsis ua haujlwm ntawm daim siab. Cov neeg mob uas tsis tshua mob hepatic tsis txaus (raws li kev faib tawm rau menyuam yaus Pugh, qhov mob hnyav ntawm 5 - 6 ntsiab lus) thiab mob siab rau hepatic tsis txaus (raws li kev faib menyuam yaus Pugh, qhov mob loj tshaj plaws> 9 ntsiab lus) tau suav nrog kev kawm. Kev sib kis ntawm liraglutide nyob rau hauv pab pawg ntawm cov neeg mob uas lub siab tsis ua haujlwm tsis yog siab dua li ntawd nyob rau hauv pab pawg ntawm cov neeg noj qab haus huv, uas qhia tau tias daim siab tsis ua rau lub chaw kho mob tseem ceeb ntawm pharmacokinetics ntawm liraglutide.
Tsis ua haujlwm:
Lub chaw muag tshuaj ntawm liraglutide tau kawm txog cov neeg mob uas ua rau lub raum tsis ua haujlwm hauv ib txoj kev tshawb nrhiav ib zaug. Txoj kev tshawb fawb no suav nrog cov ncauj lus ntawm lub raum tsis ua haujlwm: los ntawm kev mob me (kev soj ntsuam creatinine tshem ntawm 50-80 ml / min) mus rau qhov hnyav (kev ntsuas ntawm creatinine arance kev nyab xeeb ntawm cov menyuam tsis tau ua.
Cov Ntaub Ntawv Kawm Txog Kev Nyab Xeeb Kev Phom Sij
Cov txiaj ntsig ntawm kev soj ntsuam cov tshuaj lom mob lom nrog kev qhia kom rov qab ua dua ntawm cov tshuaj, suav nrog genotoxicity, pom tias kev siv liraglutide tsis ua rau muaj kev phom sij rau tib neeg kev noj qab haus huv.
Cov thyroid C-cell qog ntawm nas thiab nas tau txheeb xyuas thaum tshawb fawb 2 xyoo ntawm cov carcinogenicity ntawm cov tshuaj hauv cov nas thiab tsis ua rau tuag. Qhov koob tshuaj tsis muaj tshuaj lom (NOAEL) tsis tau tsim muaj nyob hauv nas. Qhov tshwm sim ntawm cov qog zoo li no hauv liab kho nrog liraglutide rau 20 lub hlis tsis pom. Cov txiaj ntsig tau hauv kev tshawb fawb ntawm cov nas yog txuam nrog qhov tseeb tias nas muaj kev cuam tshuam tshwj xeeb rau cov tsis-genotoxic tshwj xeeb kev kho kom haum xeeb los ntawm GLP-1 receptor. Qhov tseem ceeb ntawm cov ntaub ntawv tau txais rau tib neeg yog tsawg, tab sis tsis tuaj yeem tshem tawm tag nrho. Qhov pom ntawm lwm yam kev mob neoplasm nrog kev kho tsis tau pom.
Kev tshawb nrhiav tsiaj tseem tsis tau qhia tawm qhov cuam tshuam ncaj qha ntawm cov tshuaj ntawm kev muaj peev xwm, tab sis muaj qee qhov nce me ntsis ntawm lub cev thaum nyuam qhuav pib tuag thaum lub sij hawm kho nrog qhov ntau tshaj ntawm cov tshuaj. Cov kev qhia ntawm cov tshuaj Viktoza ® rau cov nas nyob nruab nrab ntawm lawv cev xeeb tub ua rau lawv txo lawv niam lub cev qhov hnyav thiab kev loj hlob ntawm lub plab nrog qhov tsis tiav kawm txog cov nyhuv ntawm tus tav, thiab kev hloov kho hauv cov pob txha pob txha hauv pawg neeg luav. Kev loj hlob ntawm cov me nyuam yug hauv cov pawg pab pawg tsawg zuj zus thaum kho nrog Victoza ®, thiab qhov kev txo qis no pheej mob siab rau tom qab pub mis rau hauv cov pab pawg ntawm cov qauv uas tau txais cov qib siab liraglutide. Kuj tsis paub tias muaj dab tsi ua rau muaj kev nce qib hauv kev loj hlob ntawm cov menyuam yug menyuam - qhov kev txo qis ntawm lawv cov niam cov mis noj vim muaj qhov cuam tshuam ncaj qha ntawm GLP-1, lossis cov khoom siv mis tsis txaus los ntawm leej niam vim tias cov roj calorie txo qis.

Dosage daim ntawv

Subcutaneous tov 6 mg / ml

1 ml ntawm kev daws

cov tshuaj nquag - liraglutide 6 mg,

kev tshem tawm: sodium hydrogen phosphate dihydrate, propylene glycol, phenol, hydrochloric acid (2M tov) / sodium hydroxide (tov 2M), dej rau kev txhaj tshuaj.

Pob tshab tsis muaj kob lossis yuav luag tsis muaj kev daws teeb meem, siv dawb ntawm cov tshuab tsis muaj zog.

Tsuas tshuaj thiab tswj hwm

Cov tshuaj Viktoza® tau siv ib zaug ib hnub nyob rau txhua lub sijhawm, tsis hais txog kev noj zaub mov, nws tuaj yeem raug tso tawm raws li kev txhaj tshuaj hauv qab plab, ncej lossis xub pwg. Qhov chaw thiab lub sijhawm ntawm kev txhaj tshuaj tuaj yeem sib txawv yog tsis muaj kev kho kom haum. Txawm li cas los xij, nws zoo dua los siv tshuaj ntau nyob rau tib lub sijhawm ntawm ib hnub, thaum lub sijhawm yooj yim tshaj plaws rau tus neeg mob. Cov lus qhia ntxiv ntawm cov txheej txheem ntawm kev siv tshuaj Viktoza® tuaj yeem pom nyob rau hauv seem rau kev siv thiab pov tseg. Cov tshuaj Viktoza® tsis tuaj yeem siv rau kev tswj hwm ntawm cov dej khov thiab intramuscular.

Thawj koob tshuaj Victoza® yog 0.6 mg rau ib hnub. Tom qab siv cov tshuaj rau tsawg kawg ib lub lis piam, cov koob tshuaj yuav tsum tau nce rau 1.2 mg. Muaj pov thawj tias nyob hauv qee cov neeg mob, cov txiaj ntsig ntawm kev kho mob nce nrog qhov nce ntxiv ntawm koob tshuaj los ntawm 1.2 mg rau 1.8 mg. Txhawm rau kom ua tiav qhov zoo tshaj plaws glycemic tswj nyob rau hauv tus neeg mob thiab coj mus rau hauv kev saib xyuas kev siv tshuaj, qhov tshuaj ntawm Viktoza® tuaj yeem nce ntxiv rau 1.8 mg tom qab siv nws ntawm koob tshuaj 1.2 mg rau tsawg kawg ib lub lis piam. Kev siv cov tshuaj hauv cov tshuaj txhua hnub saum toj no 1.8 mg tsis pom zoo.

Cov tshuaj Victoza® tuaj yeem siv los ntxiv rau kev kho mob uas twb muaj lawm nrog metformin lossis kev sib txuas ua ke nrog metformin thiab thiazolidinedione. Txoj kev kho nrog metformin ua ke nrog thiazolidinedione tuaj yeem txuas ntxiv nyob rau hauv koob tshuaj tam sim no.

Victoza® tuaj yeem siv los ua lub zog sib luag thaum lub sijhawm kho sulfonylurea lossis kev kho mob sib xyaw nrog metformin thiab sulfonylurea lossis basal insulin. Thaum Viktoza® raug ntxiv rau sulfonylurea lossis basal insulin txoj kev kho, koob tshuaj txo ntawm sulfonylurea lossis basal insulin yuav tsum raug txiav txim siab txhawm rau txo qhov kev pheej hmoo ntawm qhov tsis xav txo ntshav qog ntshav (saib Ntu "Cov Lus Qhia Tshwj Xeeb").

Yuav kom kho qhov koob tshuaj ntawm Victoza®, tsis tas kuaj xyuas tus kheej ntawm cov ntshav qab zib tsis tas yuav tsum muaj. Txawm li cas los xij, thaum pib ntawm kev kho mob nrog Viktoza® hauv kev sib xyaw nrog sulfonylurea derivatives lossis nrog basal insulin, xws li kev tshuaj xyuas nws tus kheej ntawm cov ntshav qabzib yuav raug kho qhov tshuaj ntawm sulfonylurea npaj.

Cov pab pawg neeg tshwj xeeb

Cov Neeg Laus (> 65 xyoo): Tsis tas yuav xaiv ib koob tshuaj nyob ntawm lub hnub nyoog. Tsuas muaj kev paub tsawg nrog kev siv cov tshuaj hauv cov neeg mob hnub nyoog 75 xyoo thiab laus dua (saib ntu "Pharmacokinetics").

Cov neeg mob uas lub raum tsis ua hauj lwm zoo

Tsis tas yuav hloov kho lub koob tshuaj rau hauv kev kho mob ntawm cov neeg mob nrog cov mob tsis zoo ntawm lub raum tsis ua haujlwm (creatinine tshem tawm 60 - 90 ml / min). Tsuas muaj kev paub tsawg kawg nkaus rau kev kho mob rau cov neeg mob raum tsis ua haujlwm (kev tsim kho lub peev xwm 30–59 ml / min) thiab tsis muaj ntaub ntawv hais txog kev kho mob rau cov neeg mob lub raum tsis ua haujlwm zoo (creatinine tshem hauv qab 30 ml / min). Tam sim no, Victoza tsis pom zoo rau kev siv los ntawm cov neeg mob uas muaj cov mob tsis zoo los sis mob ntawm lub raum, nrog rau cov neeg mob ntawm lub davhlau ya nyob twg ntawm kev mob raum (saib ntu Pharmacokinetics)

Cov neeg mob uas muaj lub siab ua haujlwm tsis zoo

Cov kev paub ntawm kev kho cov neeg mob nrog txhua daim ntawv ntawm daim siab tsis ua hauj lwm (mob me, mob hnyav thiab mob hnyav) yog tam sim no ib yam nkaus thiab txwv tsis pub siv Victoza (saib Ntu Pharmacokinetics).

Kev kuaj mob rau cov neeg mob

Cov tshuaj Victoza tsis pom zoo rau cov menyuam yaus thiab cov hluas hnub nyoog qis dua 18 xyoo vim tias tsis muaj ntaub ntawv qhia txog kev nyab xeeb thiab kev ua haujlwm ntawm nws txoj siv.

Sab sij huam

Hauv kev sim tshuaj, feem ntau qhia txog kev mob tshwm sim los ntawm txoj hnyuv: xeev siab thiab raws plab (sau hauv> 10% ntawm cov neeg mob), ntuav, cem quav, mob plab thiab dyspeptic tshwm sim (sau tseg hauv ≥ 1%, tab sis ≤ 10 % ntawm cov neeg mob).

Thaum pib kho nrog Viktoza®, cov kev mob tshwm sim ntawm txoj hnyuv no tuaj yeem tshwm sim ntau dua, tab sis raws li kev kho mob txuas ntxiv, cov tshuaj tiv thaiv feem ntau poob qis li ob peb hnub lossis ntau lub lis piam. Cov kev tsis zoo nyob rau hauv daim ntawv ntawm mob taub hau thiab mob caj pas sab hauv feem ntau tau pom tus kab mob feem ntau (1 - 10% ntawm cov neeg mob). Tsis tas li ntawd, txoj kev loj hlob ntawm hypoglycemic tej yam kev mob yog ua tau, tshwj xeeb tshaj yog thaum siv cov tshuaj Victoza® nyob rau hauv kev sib xyaw nrog sulfonylurea derivatives (sau npe hauv> 10% ntawm cov neeg mob). Cov tshuaj tiv thaiv kab mob ntshav nce siab feem ntau yog tawm tsam keeb kwm yav dhau los ntawm kev sib xyaw ua ke ntawm kev siv tshuaj Viktoza® nrog sulfonylureas.

Cov kev mob hnyav tau qhia tawm tsawg kawg.

Qhia txog cov kev phiv tshuaj rau ib tug neeg

Hauv qhov kev tshawb fawb soj ntsuam siv liraglutide raws li kev kho mob monotherapy, qhov tshwm sim ntawm hypoglycemia nrog liraglutide tsawg dua qhov tshwm sim ntawm hypoglycemia hauv cov neeg mob kho nrog kev siv yeeb tshuaj (glimepiride). Cov kev nquag tshwm sim ntau tshaj plaws muaj xws li mob plab hnyuv, kab mob, thiab kis.

Feem ntau cov kev tshwm sim uas tau lees paub tias muaj ntshav qab zib tsawg nyob hauv kev sim tshuaj kho mob tau tsis txaus ntseeg. Hauv kev tshawb nrhiav siv liraglutide li kev kho mob monotherapy, tsis muaj ib qho mob hnyav rau txo ntshav qab zib tsawg. Kev mob ntshav hnyav ntawm lub cev tsis muaj ntshav tsis tshwm sim thiab tau pom thaum xub thawj nrog kev siv liraglutide siv nrog sulfonylurea (0.02 ntu kev mob hauv ib tus neeg mob xyoo). Cov neeg mob tsawg heev (0.001 ntu kev mob hauv ib tus neeg mob lub xyoo) tau pom nrog cov thawj coj ntawm liraglutide ua ke nrog cov tshuaj tiv thaiv kab mob hauv lub cev uas tsis yog sulfonylurea. Txoj kev pheej hmoo ntawm hypoglycemia yog tsawg nrog kev sib xyaw ua ke ntawm kev siv tshuaj ntawm pob zeb insulin thiab liraglutide (1.0 ntu ib xyoo ntawm tus neeg mob, saib hauv ntu Pharmacodynamics).

Lub plab zom zaws muaj qhov tsis zoo

Thaum liraglutide thiab metformin tau sib koom ua ke, 20.7% ntawm cov neeg mob tau tshaj tawm tsawg kawg ib zaug muaj kev txhawm thiab 12.6% ntawm cov neeg mob tau tshaj tawm tsawg kawg ib zaug muaj mob zawv plab.

Thaum liraglutide sib xyaw nrog sulfonylurea, 9.1% ntawm cov neeg mob tau tshaj tawm tsawg kawg yog ib qho muaj mob ntawm xeev siab thiab 7.9% ntawm cov neeg mob tau tshaj tawm tsawg kawg yog ib qho kev mob zawv plab. Feem ntau cov kev mob tshwm sim tau mob sib khuav los yog me nyob hauv qhov thiab muaj qhov koob tshuaj.

Nrog rau kev kho mob ntev, qhov ntau thiab mob tsawg dua hauv cov neeg mob feem ntau uas muaj xeev ntuav hauv thawj theem.

Hauv cov neeg mob uas laus dua 70 xyoo, thaum kho nrog liraglutide, mob plab zom mov tuaj yeem tshwm sim ntau dua.

Hauv cov neeg mob uas mob mentsis mus rau lub raum lub raum tsis ua haujlwm (creatinine tshem tawm ntawm 60-90 ml / min thiab 30-59 ml / min, feem), ntau qhov mob plab hnyuv tawm tuaj yeem tshwm sim thaum kho nrog liraglutide.

Kev tsis suav cov neeg mob los ntawm kev sim

Hauv kev tshuaj ntsuam xyuas mus ntev (26 lub lis piam lossis ntau dua), qhov feem ntawm cov neeg mob cais tawm ntawm kev kuaj vim tias muaj kev phiv tshuaj yog 7.8% rau cov neeg mob tau txais kev kho mob nrog liraglutide thiab 3.4% rau cov neeg mob los ntawm pawg sib piv. Feem ntau cov kev phiv tshuaj uas ua rau qhov tshem tawm ntawm kev sim hauv kev kho mob ntawm cov neeg mob liraglutide suav nrog xeev siab (2.8% ntawm cov neeg mob) thiab ntuav (1.5% ntawm cov neeg mob).

Cov tshuaj tiv thaiv ntawm qhov chaw txhaj tshuaj

Cov tshuaj tiv thaiv nyob rau ntawm qhov chaw txhaj tshuaj ntawm cov tshuaj tau tshaj tawm kwv yees li ntawm 2% ntawm cov neeg mob thaum lub sijhawm tshuaj xyuas mus ntev uas raug soj ntsuam ntawm Victoza (26 lub lis piam lossis ntau dua). Cov kev mob tshwm sim feem ntau tseem me.

Lub sijhawm ntev los tswj cov kab mob kev nkeeg ntawm Victoza (26 lub lis piam lossis ntau dua), tau tshaj tawm tias muaj qee tus neeg muaj tus mob ua rau muaj tus mob ua xua (

Cov Yuav Tsum Muaj

- Ua haujlwm kom yuag rau cov tshuaj nquag lossis lwm yam

cov cheebtsam uas tsim cov tshuaj

- siv hauv cov neeg mob uas muaj ntshav qab zib hom 1

- rau kev kho mob ntshav qab zib ketoacidosis

mob raum thiab mob hepatic tsis ua haujlwm

- menyuam yaus thiab tub ntxhais hluas muaj hnub nyoog txog 18 xyoo

- cev xeeb tub thiab lactation

Cov tshuaj sib cuam tshuam

Hauv tshuaj ntsuam xyuas tshuaj vitro

Liraglutide qhia txog kev muaj peev xwm tsawg rau kev sib txuam tshuaj pharmacokinetic vim muaj cov metabolism hauv lub cytochrome P-450 (CYP), nrog rau kev khi rau cov ntshav protein.

Hauv vivo tshuaj ntsuam kev sib cuam tshuam

Kev qeeb me ntsis ntawm lub plab zom mov thaum siv liraglutide tuaj yeem cuam tshuam qhov nqus ntawm cov tshuaj sib xyaw uas tau npaj rau kev tswj hwm qhov ncauj. Cov kev tshawb fawb txog kev sib txuas yeeb tshuaj tsis tau pom tias muaj kev poob qis me ntsis hauv kev nqus ntawm cov tshuaj no. Coob tus neeg mob tau kho nrog Victoza® muaj yam tsawg ib zaug mob raws plab. Kev mob plab zawv tuaj yeem cuam tshuam rau kev nqus ntawm cov tshuaj hauv qhov ncauj uas siv tib lub sijhawm nrog Victoza®.

Warfarin thiab lwm yam tshuaj txuas rau kev txij nkawm

Cov kev tshawb fawb txog kev sib cuam tshuam ntawm ob lub tshuaj tsis tau ua. Thaum pib ntawm kev kho mob nrog Victoza® hauv cov neeg mob uas tau txais warfarin lossis lwm tus kabmob ntawm cov txij nkawm, nws raug nquahu kom kuaj xyuas INR (International Kev Sib Raug Zoo) ntau zaus.

Liraglutide tsis ua rau muaj kev hloov pauv rau kev ua txhua yam ntawm cov tshuaj paracetamol tom qab nws tswj hwm hauv ib koob li 1000 mg. Qhov siab tshaj plaws ntawm paracetamol hauv ntshav (Cmax) poob qis los ntawm 31%, thiab lub sijhawm nruab nrab mus cuag lub ncov siab hauv nws qhov kev mob siab (tmax) hauv cov ntshav ntshav tau txuas ntxiv los ntawm 15 feeb. Nrog rau kev tswj hwm ib txhij ntawm cov kab mob liraglutide thiab paracetamol, kev kho kom haum rau tom kawg kuj tsis tas yuav ua haujlwm.

Liraglutide tsis ua rau thaj chaw muaj kev hloov pauv ntau hauv cov txiaj ntsig ntawm atorvastatin tom qab nws txoj kev tswj hwm hauv ib zaug ntawm 40 mg. Yog li, kev hloov kho tshuaj atorvastatin thaum noj Victoza® tsis tas yuav ua. Qhov siab tshaj plaws ntshav plasma concentration ntawm atorvastatin (Cmax) poob qis los ntawm 38%, thiab lub sijhawm nruab nrab mus cuag lub ncov ntshav plasma concentration (tmax) hauv cov neeg mob tau txais liraglutide lengthened los ntawm ib mus txog peb teev.

Liraglutide tsis ua rau muaj kev hloov pauv rau qhov muaj txiaj ntsig ntawm griseofulvin tom qab kev coj nws hauv ib koob tshuaj 500 mg. Qhov siab tshaj plaws ntawm griseofulvin (Cmax) tau nce 37%, thaum lub sijhawm nruab nrab kom mus txog nws cov ntsiab lus siab tshaj plaws (tmax) hauv ntshav tsis pauv. Koob tshuaj hloov kho ntawm griseofulvin thiab lwm yam tshuaj muaj solubility qis thiab siab permeability tsis tas yuav.

Kev qhia ntawm digoxin nyob rau hauv ib koob tshuaj 1 mg nrog kev siv liraglutide qhia tau txo qis thaj chaw hauv qab nkhaus (AUC) ntawm digoxin los ntawm 16%, qhov siab tshaj plaws ntshav plasma concentration (Cmax) ntawm digoxin tsawg dua 31%. Lub sijhawm nruab nrab kom ncav cuag lub siab tshaj plaws (tmax) ntawm digoxin thaum noj liraglutide ntau ntxiv ntawm ib mus rau ib thiab ib nrab teev. Raws li cov txiaj ntsig tau los, kev hloov kho tshuaj ntawm digoxin thaum noj liraglutide tsis tas yuav tsum ua.

Kev tswj hwm ntawm lisinopril nyob rau hauv ib koob tshuaj 20 mg thaum siv liraglutide qhia tias qhov txo qis hauv thaj chaw hauv qab qhov nkhaus (AUC) ntawm lisinopril los ntawm 15%, qhov siab tshaj plaws ntshav plasma concentration (Cmax) ntawm lisinopril txo 27 feem pua. Lub sijhawm nruab nrab kom ncav cuag lub siab tshaj plaws (tmax) ntawm lisinopril hauv ntshav thaum noj liraglutide ntau ntxiv los ntawm rau mus rau yim teev. Raws li qhov tshwm sim, kev kho pob tshuaj lisinopril thiab digoxin thaum noj tshuaj liraglutide tsis tas yuav tsum ua.

Qhov siab tshaj plaws ntshav plasma concentration (Cmax) ntawm ethinyl estradiol thiab levonorgestrel hauv kev kho mob ib zaug thaum kho nrog liraglutide poob los ntawm 12% thiab 13%, feem. Nyob rau hauv tib co mob, lub sij hawm nruab nrab kom ncav cuag lub siab tshaj plaws (tmax) ntawm cov tshuaj no yog 1.5 teev tom qab tshaj li niaj zaus. Clinically muaj txiaj ntsig rau tag nrho cov txiaj ntsig ntawm ethinyl estradiol thiab levonorgestrel hauv lub cev tsis muaj liraglutide. Yog li, qhov kev cia siab ua kom muaj txiaj ntsig zoo ntawm ob qho tshuaj thaum lub sij hawm kho nrog liraglutide tsis hloov.

Tsis muaj cov tshuaj pharmacokinetic lossis pharmacodynamic sib xyaw ntawm liraglutide nrog insulin detemir tau tshawb pom nrog kev siv tshuaj insulin ib zaug ntawm 0.5 U / kg nrog liraglutide ntawm koob tshuaj 1.8 mg rau cov neeg mob uas muaj ntshav qab zib hom 2 mellitus.

Cov yeeb tshuaj ntxiv rau hauv Victoza® yuav ua rau muaj kev paug liraglutide. Txij li kev tshuaj ntsuam sib txawv tsis tau nqa tawm, Viktoza® tsis tuaj yeem sib xyaw nrog lwm cov tshuaj, suav nrog kev daws teeb meem.

Cov lus qhia tshwj xeeb

Victoza® yuav tsum tsis txhob siv rau cov neeg mob uas muaj ntshav qab zib hom 1 los yog siv rau kev kho mob ntshav qab zib ketoacidosis.

Victoza® tsis hloov cov insulin.

Cov kev paub dhau los ntawm kev siv Victoza® rau cov neeg mob uas lub plawv tsis ua haujlwm ntawm I-II cov chav kawm ua haujlwm tau raws li Kev Ua Haujlwm Sib Tw ntawm Lub Ntev Mob Ua Tsis Txaus (CHF) ntawm New York Cardiology Association (NYHA) yog qhov tsawg thiab yog li liraglutide yuav tsum siv nrog ceev faj. Tsis muaj kev paub dhau los hauv kev kho mob rau cov neeg mob siab tsis txaus lub siab ntawm chav kawm III - IV raws li NYHA kev faib tawm thiab yog li kev teem caij liraglutide hauv cov neeg mob zoo li no tsis pom zoo.

Cov ntaub ntawv hais txog kev siv tshuaj Viktoza® nyob rau hauv cov neeg mob muaj mob plab hnyuv thiab mob ntshav qab zib paresis ntawm lub plab yog txwv, kev siv tshuaj Viktoza® hauv cov pab pawg neeg mob tsis pom zoo. Kev siv cov tshuaj Viktoza® cuam tshuam nrog kev txhim kho ntawm lub sijhawm tsis zoo tshwm sim los ntawm txoj hnyuv, xws li xeev siab, ntuav thiab raws plab.

Kev siv ntawm lwm cov GLP-1 agonists tau cuam tshuam nrog kev pheej hmoo ntawm kev tsim mob pancreatitis. Muaj ntau tus neeg mob ua mob pancreatitis tau tshaj tawm. Cov neeg mob yuav tsum tau qhia paub txog cov yam ntxwv ntawm tus yam ntxwv ntawm kev loj hlob ntawm tus mob huam: mob tsis haum hnyav hauv plab. Yog tias pom muaj tus mob pancreatitis, txoj kev kho mob nrog Victoza® thiab lwm yam tshuaj txaus ntshai yuav tsum nres tam sim ntawd.

Thaum paub tseeb tias kev kuaj mob ntawm tus mob hnoos qhuav, kev siv tshuaj Viktoza® yuav tsum tsis txhob rov ua dua tshiab. Kev ceev faj yuav tsum tau siv thaum kev sau daim ntawv tshuaj rau cov neeg mob uas muaj keeb kwm ntawm pancreatitis.

Mob qog noj ntshav

Thaum lub sijhawm kev sim tshuaj ntawm cov tshuaj Victoza®, cov thyroid phiv tau tshaj tawm, suav nrog txhawb cov ntshav calcitonin, diffuse thyrotoxic goiter thiab thyroid neoplasms, yog li liraglutide yuav tsum siv nrog ceev faj, tshwj xeeb tshaj yog nyob rau cov neeg mob uas muaj cov kab mob ua ntej. lub qog ua haujlwm (saib ntu "Cuam Tshuam").

Cov neeg mob noj liraglutide sib xyaw nrog sulfonylurea lossis insulin basal yuav muaj kev pheej hmoo ntau hauv lub qog ntshav qab zib (saib ntu "Cov Kev Phiv"). Txoj kev pheej hmoo ntawm ntshav qog tuaj yeem txo los ntawm kev txo qis ntawm sulfonylurea lossis basal insulin.

Cov cim thiab tsos mob ntawm lub cev qhuav dej, nrog rau lub raum tsis ua haujlwm thiab mob raum tsis ua haujlwm, tau piav qhia hauv cov neeg mob noj liraglutide. Cov neeg mob noj liraglutide yuav tsum qhia txog kev pheej hmoo ntawm kev ua kom lub cev qhuav dej yog nyob ntawm kev phiv los ntawm lub plab zom mov thiab pom zoo tias yuav tsum ceev faj kom tiv thaiv tsis ua kua dej hauv lub cev.

Cov Ntaub Ntawv Kawm Txog Kev Nyab Xeeb Kev Phom Sij

Cov txiaj ntsig ntawm kev tshawb fawb, raws li feem ntau lees paub cov kev tshawb fawb ntawm kev nyab xeeb pharmacological, kev mob toxicity nrog rov qab ntau dua ntawm cov tshuaj thiab genotoxicity, qhia tau hais tias kev siv liraglutide tsis ua rau tib neeg txoj kev noj qab haus huv.

Neoplasms ntawm nas cov qog caj pas C-hlwb thiab nas tau kuaj pom thaum ob-xyoos sim ntawm oncogenicity ntawm cov tshuaj hauv cov nas thiab tsis ua rau tuag. Tsis muaj cov pov thawj ntawm cov kev mob tshwm sim tsis zoo (NOAEL) tau pom ntawm cov nas. Qhov pom ntawm neoplasms hauv cov liab tau kho nrog liraglutide rau 20 lub hlis tsis pom. Cov txiaj ntsig tau hauv kev tshuaj ntsuam ntawm cov nas muaj feem xyuam nrog qhov tseeb tias nas muaj kev cuam tshuam tshwj xeeb rau cov receptor-mediated glucagon-zoo li peptide-1 (GLP-1) ntawm cov tsis-genotoxic tshwj xeeb mechanism. Qhov tseeb ntawm cov ntaub ntawv tau txais rau tib neeg yog tsawg, tab sis tsis tuaj yeem tshem tawm tag nrho. Qhov pom ntawm lwm yam kev mob neoplasm nrog kev kho tsis tau pom.

Hauv kev tshawb xyuas tsiaj, tsis muaj qhov cuam tshuam ncaj qha ntawm cov tshuaj ntawm kev muaj peev xwm, tab sis muaj qhov nce me ntsis ntawm cov zaus ntawm thaum ntxov embryonic kev tuag thaum kho nrog ntau tshaj plaws ntawm cov tshuaj. Kev qhia txog cov tshuaj Viktoza rau cov nas nyob nruab nrab ntawm lub sijhawm xeeb tub ua rau muaj kev txo qis ntawm lawv niam lub cev qhov hnyav thiab kev loj hlob ntawm lub plab nrog qhov tsis tiav kawm txog cov nyhuv ntawm tus tav, thiab kev hloov pauv ntawm cov pob txha pob txha hauv pawg neeg luav. Kev loj hlob ntawm cov menyuam mos nyob rau hauv cov pab pawg ntawm cov nas thaum kho nrog Victoza poob qis, thiab qhov no tseem pheej nyob rau lub sijhawm tom qab pub niam mis rau hauv cov pab pawg ntawm cov qauv uas tau txais cov qib siab liraglutide. Tsis paub tias muaj dab tsi ua rau muaj kev nce qib hauv kev loj hlob ntawm cov menyuam mos yug menyuam - qhov kev noj ntawm niam cov kua mis ntau dua vim qhov cuam tshuam ncaj qha ntawm cov glucagon-zoo li peptide GLP-1, lossis cov khoom noj niam mis tsis muaj txiaj ntsig los ntawm cov niam menyuam vim tias kev noj zaub mov zoo rau lawv cov calories.

Tom qab txhaj tshuaj liraglutide hauv luav, mob me me mus txog ntuav, liab, thiab o ntawm thaj chaw txhaj tshuaj.

Siv thaum cev xeeb tub thiab thaum pub niam mis

Kev tshawb nrhiav tsiaj tseem tsis tau qhia tawm qhov cuam tshuam ncaj qha ntawm cov tshuaj ntawm kev muaj peev xwm, tab sis muaj qee qhov nce me ntsis ntawm lub cev thaum nyuam qhuav pib tuag thaum lub sij hawm kho nrog qhov ntau tshaj ntawm cov tshuaj. Kev tswj hwm ntawm Viktoza® rau cov nas nyob nruab nrab ntawm lawv cev xeeb tub ua rau muaj kev txo lawv niam lub cev hnyav thiab kev loj hlob ntawm lub cev nrog qhov tsis tiav kawm txog cov pob txha, thiab kev hloov kho ntawm pob txha caj dab hauv cov pab pawg neeg luav. Kev loj hlob ntawm cov menyuam mos yug hauv cov pawg pab pawg thaum lub sijhawm kho nrog Victoza® poob qis, thiab qhov no txo qis txuas ntxiv tom qab pub niam mis hauv cov pab pawg ntawm cov tib neeg tau txais liraglutide ntau dua. Tsis paub tias muaj dab tsi ua rau muaj kev nce qib hauv kev loj hlob ntawm cov menyuam mos yug menyuam yaus - qhov kev txo qis ntawm lawv niam cov kua mis vim muaj qhov cuam tshuam ncaj qha ntawm GLP-1, lossis qhov tsis txaus ntawm kev tsim cov kua mis tawm los ntawm leej niam vim muaj kev txo qis hauv lawv cov calorie kom tsawg.

Cov ntaub ntawv zoo txaus ntawm kev siv tshuaj yeeb siv Victoza® hauv cov poj niam cev xeeb tub tsis muaj. Peb paub tsis meej tias yuav muaj xwm txheej dabtsi rau tib neeg.

Cov tshuaj Viktoza® tuaj yeem siv tsis tau thaum cev xeeb tub, hloov, nws pom zoo kom ua tiav kev kho mob nrog insulin. Yog tias tus neeg mob tseem tabtom npaj cev xeeb tub, lossis lub cev xeeb tub twb pib lawm, kev kho mob nrog Victoza® yuav tsum nres tam sim ntawd.

Tsis muaj kev paub dhau los ntawm kev siv tshuaj yeeb yaj yeeb Victoza® nyob rau hauv cov poj niam laus, kev siv cov tshuaj thaum lub sijhawm pub niam mis yog contraindicated.

Cov yam ntxwv ntawm cov nyhuv ntawm cov tshuaj ntawm lub peev xwm tsav tsheb thiab lub phom sij phom sij

Qhov kev tshawb nrhiav txog qhov tshwm sim ntawm cov tshuaj Victoza® ntawm kev muaj peev xwm tsav tsheb thiab kev ua haujlwm nrog cov txheej txheem tsis tau ua. Cov neeg mob yuav tsum tau ceeb toom tias lawv yuav tsum ceev faj kom tsis txhob muaj kev txhim kho hauv lub xeev ntawm lub qog ntshav qab zib thaum tsav tsheb thiab thaum ua haujlwm nrog cov txheej txheem, tshwj xeeb tshaj yog tias Victoza® raug coj los ua ib feem ntawm kev sib xyaw nrog kev kho nrog sulfonylureas lossis nrog insulin basal.

Noj ntau dhau

Cov tsos mob: thaum lub sijhawm kev soj ntsuam ntawm Victoza®, ib qho ntawm cov neeg mob ntshav qab zib hom 2 tau raug kev txom nyem ntau dhau ntawm cov tshuaj nyob rau hauv qhov kev txhaj tshuaj subcutaneous ntawm koob tshuaj 72 mg (40 zaug qhov siab tshaj qhov xav tau ntawm 1.8 mg). Kev haus ntau dhau ua rau xeev siab thiab ntuav. Tsis tau sau tseg tias muaj qog ntshav qab zib tsawg. Tus neeg mob zoo tu qab hlo yam tsis muaj teeb meem.

Txoj kev kho mob: pom zoo kom kho cov tsos mob kom zoo, nyob ntawm qhov chaw kuaj mob thiab cov tsos mob.

Cov Tshuaj Hauv Tshuaj

Liraglutide yog ib qho khoom noj tsis haum ntawm tib neeg GLP-1 (glucagon-zoo li peptide-1). Ua los ntawm cov txheej txheem biotechnology ntawm kev tso tawm DNA (deoxyribonucleic acid) siv Saccharomyces cerevisiae lim, uas muaj 97% homology nrog tib neeg GLP-1, khi thiab ua kom GLP-1 receptors hauv tib neeg.

GLP-1 receptor yog lub hom phiaj rau haiv neeg GLP-1, uas yog endogenous hormone ntawm incretin, uas ua rau cov piam thaj hauv insulin secretion hauv pancreatic cells-hlwb. Piv nrog cov haiv neeg GLP-1, cov pharmacodynamic thiab pharmacokinetic profiles ntawm liraglutide tso cai nws yuav tsum tau noj ib hnub ib zaug.

Nrog kev txhaj tshuaj subcutaneous, qhov ntev ua haujlwm ntawm qhov quav yeeb tshuaj yog raws peb txoj kev ua haujlwm:

kev sib koom tes tus kheej, uas muab ncua ntev liraglutide,
khi rau albumin,
qib siab ntawm enzymatic ruaj khov tiv thaiv DPP-4 (dipeptidyl peptidase-4) thiab NEP (enzyme nruab nrab endopeptidase), uas ua kom T ntev_1/2 (ib nrab-lub neej) ntawm ib yam khoom los ntawm ntshav ntshav.

Cov txiaj ntsig ntawm liraglutide yog ua raws li kev sib cuam tshuam nrog cov kis tshwj xeeb GLP-1, raws li cov txiaj ntsig ntawm theem uas cAMP (cyclic adenosine monophosphate) nce. Raws li kev txiav txim ntawm cov tshuaj, glucose-dependent stimulation ntawm insulin secretion yog pom, thiab kev ua haujlwm ntawm pancreatic cells-cells txhim kho. Nyob rau tib lub sijhawm, piam thaj-kev tsuj ntshav ntawm kev cuam tshuam ntau dhau kev tso ua ke ntawm glucagon tshwm sim. Yog li, nrog kev nce ntxiv hauv cov concentration ntawm cov ntshav qabzib, glucagon secretion yog suppressed thiab insulin secretion yog tsa.

Ntawm qhov tod tes, hauv cov neeg mob hypoglycemia, liraglutide txo qis cov tshuaj insulin tsis muaj cov tshuaj tiv thaiv glucagon tso pa tawm. Tus txheej txheem rau kev txo qis glycemia tseem suav nrog kev qeeb me ntsis hauv kev ua kom lub plab zom mov. Siv cov txheej txheem uas ua rau txo qis kev tshaib plab thiab txo qis hauv kev siv lub zog, liraglutide ua rau txo qis nqaij adipose thiab poob phaus.

GLP-1 yog lub zog tswj kev ua kom qab los noj mov thiab cov khoom noj uas muaj calorie, lub receptors ntawm no peptide nyob rau ntau thaj chaw ntawm lub paj hlwb uas koom nrog cov kev cai ntawm lub qab los noj mov.

Thaum ua cov kev tshawb fawb tsiaj, nws tau pom tias los ntawm kev ua kom tshwj xeeb ntawm GLP-1 receptors, liraglutide ua rau cov cim kev ua kom meej dua thiab ua kom lub cev ua kom tsis muaj zog, ua rau poob phaus.

Tsis tas li, raws li cov kev tshawb fawb tsiaj, liraglutide qeeb kev loj hlob ntawm cov ntshav qab zib. Cov tshuaj yog qhov ua tau zoo nyob rau hauv kev tshwj xeeb ntawm kev tua kab mob hlwb (pancreatic cell-cell proliferation) thiab tiv thaiv kev tuag ntawm β-hlwb (apoptosis), uas yog ntxias los ntawm cytokines thiab cov roj dawb. Yog li, liraglutide nce insulin biosynthesis thiab nce β-cell ntau. Tom qab normalizing cov piam thaj hauv siab, liraglutide nres nce qhov ntau ntawm pancreatic β-cells.

Cov neeg muaj yeej muaj lub sijhawm ntev 24-teev thiab hloov kho glycemic, uas yog ua tiav los ntawm kev txo qis ntawm kev saib xyuas ntawm cov roj ntsha sai thiab tom qab noj mov nrog hom 2 ntshav qab zib.

Pharmacological pawg

Lwm yam tshuaj hypoglycemic, nrog rau kev zam ntawm cov tshuaj insulin.

Tus lej ATC A10V X07.

Victoza® yog siv los kho hom II mob ntshav qab zib mellitus rau cov neeg laus thiaj li ua tiav glycemic tswj nrog:

metformin lossis sulfonylurea hauv cov neeg mob tsis zoo glycemic tswj, txawm hais tias siv cov tshuaj tiv thaiv ntau tshaj plaws ntawm metformin lossis sulfonylurea raws li monotherapy,
metformin thiab sulfonylureas, lossis metformin thiab thiazolidinediones hauv cov neeg mob tsis zoo glycemic tswj txawm hais tias kev kho ob npaug.

Kev sib xyaw ua ke nrog cov tshuaj insulin basal hauv cov neeg mob uas tsis ua tiav glycemic tswj nrog kev pab ntawm Viktoza thiab metformin.

Kev phiv tshuaj

Hauv tsib qhov loj, ntev mus kuaj mob, ntau dua 2500 tus neeg mob tau txais Victoza® ib leeg lossis nws cov tshuaj ua ke nrog metformin, nrog glimepiride (nrog lossis tsis muaj metformin), sulfonylurea (nrog lossis tsis muaj metformin), lossis nrog metformin + rosiglitazone.

Kev ntsuas ntawm qhov tshwm sim ntawm cov kev mob tshwm sim tau nqa tawm ntawm cov ntsuas hauv qab no: ntau zaus

(≥ 1/10), feem ntau (los ntawm ≥ 1/100 txog ® - 2501). Cov kev tshwm sim tsis zoo hauv qab no tau nthuav tawm, qhov xwm txheej uas nyob hauv pab pawg ntawm cov neeg mob tau txais tshuaj Viktoza® ntau dua los ntawm ntau dua 5% ntau zaus hauv cov pab pawg uas lawv tau txais kev sib piv yeeb tshuaj. Cov kev phiv tshuaj tiv thaiv kuj suav nrog, qhov tshwm sim ntawm uas yog %1%, tab sis lawv tshwm sim ntau dua 2 zaug ntau zaus hauv kev sib piv nrog cov tshuaj sib piv.

Kev ntshaib plab thiab zaub mov tsis haum: feem ntau - hypoglycemia, anorexia, qab los noj tsis qab hau - lub cev qhuav dej *.

Kev Mob Lub Cev Tsis Txaus Siab: feem ntau - mob taub hau, kiv taub hau.

Digestive mob: nquag - xeev siab, raws plab, feem ntau - ntuav, dyspepsia, mob lub plab sab sauv, cem quav, mob plab, mob plab, mob plab, txhaws qa, mob plab zom zaws, mob plab, mob plab, mob hniav, kis mob rau lub plab. mob caj pas).

Mob plawv: feem ntau - lub plawv dhia (HR).

Kev Raug Mob Loj: tsis tshua muaj kev phiv tshuaj anaphylactic.

Cov kab mob thiab kis: feem ntau - mob khaub thuas ntawm txoj hlab ua pa (nasopharyngitis, mob ntsws).

Kev cuam tshuam dav dav thiab mob ntawm qhov chaw txhaj tshuaj: tsis ncaw - malaise, feem ntau - qaug zog, kub taub hau, tawm tsam ntawm qhov chaw txhaj tshuaj.

Mob raum thiab mob txeeb zig : rau lub raum - mob raum tsis ua haujlwm *, mob raum raum ua haujlwm *.

Ntawm feem ntawm daim tawv nqaij thiab cov nqaij mos : feem ntau - ua pob, ua npaws - urticaria, khaus.

(* Saib Ntu Ntawv Cim Ntu).

Qhia txog cov kev phiv tshuaj rau ib tug neeg

Thaum lub sijhawm kev sim tshuaj mob Viktoza® monotherapy monotherapy, qhov kev pheej hmoo ntawm hypoglycemia hauv cov neeg mob noj Victoza® tau qis dua li ntawm cov neeg mob uas tau txais cov tshuaj nquag (glimepiride). Qhov tshwm sim ntau tshaj plaws tshwm sim yog lub plab zom mov, kis tus kab mob thiab ntsaws.

Feem ntau sau tseg thaum kuaj mob, pom tias cov ntshav qab zib tsawg yog qhov tseem ceeb. Thaum lub sij hawm monotherapy nrog Viktoza®, tsis muaj ib qho teeb meem ntawm kev mob ntshav qab zib tsawg. Kev mob ntshav qis heev tshwm sim tsis tshua muaj thiab feem ntau pom nrog kev kho mob nrog Viktoza® thiab sulfonylurea (0.02 mob / neeg mob-xyoo). Tsis tshua muaj (0.001 mob / neeg mob-xyoo) muaj cov neeg mob hypoglycemia thaum kho mob Victoza® nrog lwm cov tshuaj tiv thaiv kab mob hauv lub qhov ncauj (i.e. tsis nrog sulfonylurea).

Tom qab kev siv tshuaj ntxiv ntawm cov tshuaj insulin rau kev ua rau cov neeg mob, lawv tau txais liraglutide 1.8 mg metformin; tsis muaj ib qho xwm txheej ntawm tus mob ntshav qab zib tsawg. Qhov xwm txheej ntawm cov ntshav qog ntshav nce siab yog 0.286 kis rau tus neeg mob ib xyoos. Hauv cov pab pawg sib piv, qhov kev tshwm sim ntawm kev mob ntshav qab zib tsawg yog 0.029 mob hauv ib tus neeg mob-xyoo hauv kev kho mob nrog liraglutide

1.8 mg thiab 0.129 mob ib tus neeg mob-xyoo nrog metformin kho mob.

Kev mob plab zom mov

Feem ntau ntawm kev xeev siab yog mob me lossis mob ib ntus, ib ntus thiab tsis tshua tau ua rau tshem tawm txoj kev kho.

Nrog kev kho mob sib xyaw nrog Victoza® thiab metformin, xeev siab tshwm sim tsawg kawg ib zaug hauv 20.7% ntawm cov neeg mob, thiab zawv plab hauv 12.6% ntawm cov neeg mob. Thaum muab sib xyaw nrog Viktoza® thiab sulfonylurea, xeev siab tshwm sim tsawg kawg ib zaug hauv 9.1% ntawm cov neeg mob, thiab mob plab zom mov hauv 7.9%. Feem ntau ntawm cov mob nyhav me me lossis mob nyhav thiab tau txhaj tshuaj ntau.

Hauv cov neeg mob uas muaj hnub nyoog tshaj 70 xyoo, mob plab zom mov yuav tshwm sim nrog kev kho mob nrog Victoza®.

Hauv cov neeg mob uas tsis muaj lub raum tsis ua haujlwm (kev tsim kho lub peev xwm ntawm cle 60-90 ml / min), cov teeb meem ntawm lub plab zom mov yuav tshwm sim ntau dua nrog kev kho nrog Viktozato.

Kev thum yeeb tshuaj

Lub sijhawm tswj kev tshuaj xyuas ntev ntev (26 lub sijhawm lossis ntev dua), lub sijhawm ntawm kev tshem tawm ntawm cov tshuaj Viktoza® vim muaj kev phiv tshuaj uas tau tshwm sim yog 7.8%, thiab qhov tshem tawm ntawm kev siv tshuaj yeeb yog 3.4%. Feem ntau ua rau qhov no rau cov neeg mob tau txais Victoza® yog xeev siab (2.8%) thiab ntuav (1.5%).

Vim tias lub peev xwm tiv thaiv kab mob ntawm cov tshuaj uas muaj cov protein lossis peptides, cov tshuaj tiv thaiv-liraglutidn tuaj yeem tsim nyob rau hauv cov neeg mob kho nrog Victoza®. Lawv tau tshawb pom nyob hauv nruab nrab ntawm 8.6% ntawm cov neeg mob. Qhov tsim cov tshuaj tiv thaiv tsis muaj kev cuam tshuam nrog txo qis kev ua haujlwm ntawm Victoza®.

Kev txhaj tshuaj ntawm qhov chaw

Hauv cov kev sim mus ntev ntev (26 lub lis piam lossis ntev dua), cov tshuaj tiv thaiv ntawm thaj chaw txhaj tshuaj ntawm Viktoza® tau tshaj tawm li thaj tsam li 2% ntawm cov neeg mob. Cov kev mob tshwm sim feem ntau yog mob me.

Hauv kev sim ua lub sijhawm ntev, ntau qhov xwm txheej tau tshaj tawm thaum lub sijhawm kho nrog Viktoza neither (® tsis tau tsim los tsis suav nrog).

Lub qog ua hauj lwm tsis zoo

Tag nrho cov tshwm sim ntawm cov thyroid kawg lub sij hawm tag nrho cov kev tshawb fawb (nruab nrab thiab ntev) yog 33.5, 30.0 thiab 21.7 tus neeg mob rau 1000 tus neeg mob-xyoo ntawm tag nrho cov teeb meem ntawm liraglutides, placebo thiab kev sib piv tshuaj, nrog 5.4 , 2.1 thiab 0.8 tus neeg, ntsig txog, tau pom tias yog cov kev txhaum loj heev.

Hauv cov neeg mob kho nrog Victoza®, cov qog ua cov hlav ntshav, nce qib calcitonin hauv cov ntshav, thiab cov leeg ntshav feem ntau tau sau tseg.

Tom qab pib ntawm Victoza® ntawm kev ua lag luam, kev tawm tsam tsis haum, suav nrog urticaria, pob xoo, thiab mob pob khaus, tau tshaj tawm. Ntau kis ntawm anaphylactic nrog rau cov tsos mob ntxiv xws li hypotension, palpitations, dyspnea, thiab edema kuj tau tshaj tawm.

Siv thaum cev xeeb tub thiab lactation

Cov ntaub ntawv txaus qhia txog kev siv tshuaj Viktoza® los ntawm cov poj niam cev xeeb tub tsis muaj. Cov kev tshawb fawb tsiaj tau qhia txog kev muaj menyuam yaus (saib Ntu "Cov Ntaub Ntawv Kev Nyab Xeeb Kev Nyab Xeeb"). Peb paub tsis meej tias yuav muaj xwm txheej dabtsi rau tib neeg.

Cov tshuaj Viktoza® yuav tsum tsis txhob siv thaum cev xeeb tub, nws raug nquahu kom siv tshuaj insulin hloov. Yog tias tus neeg mob xav xav cev xeeb tub lossis cev xeeb tub, ces yuav tsum tsis siv cov tshuaj Victoza. Txuas ntxiv.

Lub sijhawm lactation

Kuj tsis paub meej tias yog liraglutide ua rau niam mis tso. Kev tshawb fawb tsiaj pom tias muaj cov roj ntsha tsis txaus thiab nws cov roj ntsha muaj peev xwm ua tau rau hauv mis. Vim tias kev paub tsis txaus thaum pub niam mis, cov tshuaj Viktoza® yuav tsum tsis txhob siv.

Vim tias cov ntaub ntawv tsis muaj, Victoza® tsis pom zoo rau menyuam yaus.

Daim ntawv thov nta

Victoza® tsis yog siv los kho cov neeg mob ntshav qab zib hom 1 mob ntshav qab zib metitus lossis mob ntshav qab zib ketoacidosis.

Viktoza® tsis hloov pauv cov tshuaj insulin.

Qhov kev ua tau zoo ntawm kev tau txais tshuaj ntxiv ntawm liraglutide hauv cov neeg mob uas twb tau txais kev kho mob nrog lawm, thiab tsis raug ntsuas.

Cov kev paub ntawm kev kho cov neeg mob uas muaj lub siab tsis ua hauj lwm ntawm I-II cov chav kawm (raws li kev faib tawm ntawm New York Association of Cardiology - NYHA) muaj tsawg, thiab tsis muaj ntaub ntawv qhia txog kev kho mob rau cov neeg mob uas muaj lub siab tsis haum ntawm III-IV cov chav kawm.

Vim muaj kev paub tsawg, nws tsis pom zoo kom muab cov tshuaj Viktoza® rau cov neeg mob ua mob hnyuv thiab mob ntshav qab zib.

Kev siv lwm yam duab ntawm GLP-1 cuam tshuam nrog kev pheej hmoo ntawm kev txhim kho pancreatitis. Muaj ntau cov ntaub ntawv qhia ntawm kev mob nrawm. Cov neeg mob yuav tsum tau qhia txog cov yam ntxwv ntawm tus yam ntxwv ntawm tus mob ua paug (txhawm, mob hnyav hauv plab plab). Yog tias pom muaj tus mob pancreatitis, txoj kev kho mob Viktoza® thiab lwm yam tshuaj lom neeg yuav tsum tsis ua ntxiv.

Thaum kuaj mob, pom tias muaj kev phiv tshuaj los ntawm cov thyroid caj pas yog qhov nce ntawm qib ntawm calcitonin hauv cov ntshav, cov leeg ntshav thiab qog, tshwj xeeb tshaj yog rau cov neeg mob uas muaj cov thyroid kab mob (saib ntu "Cov Kev Phom Sij").

Cov neeg mob tau kho nrog Victoza® tau ntsib cov tsos mob ntawm lub cev qhuav dej, nrog rau lub raum tsis ua haujlwm thiab mob raum tsis ua haujlwm.

Cov neeg mob uas tau mob rau lub nroog Victoza® yuav tsum ceeb toom txog qhov ua kom lub cev qhuav dej vim yog lub cev ua kom lub cev tsis ua haujlwm thiab yuav tsum muaj kev ceev faj rau lub cev qhuav dej.

Hauv cov neeg mob uas tau txais cov tshuaj Viktoza® ib txhij nrog sulfonylurea, txoj kev pheej hmoo ntawm kev mob hypoglycemia tau nce (saib ntu "Cov Kev Phom Sij"). Txoj kev pheej hmoo ntawm kev mob ntshav qab zib tuaj yeem txo los ntawm kev txo qis ntawm sulfonylurea.

Lub peev xwm los cuam tshuam cov tshuaj tiv thaiv tus nqi thaum tsav tsheb lossis lwm yam txheej txheem

Cov kev tshawb fawb ntawm cov nyhuv ntawm cov tshuaj Victoza® ntawm kev muaj peev xwm tsav tsheb thiab lwm cov txheej txheem tsis tau ua. Cov neeg mob yuav tsum tau qhia rau kev ntsuas kom tiv thaiv qhov tshwm sim ntawm kev mob ntshav qab zib thaum lub sijhawm tsav tsheb lossis lwm yam, tshwj xeeb tshaj yog thaum siv cov tshuaj Viktoza® ib txhij nrog sulfonylurea.

Kev sib cuam tshuam nrog lwm yam tshuaj thiab lwm yam kev sib cuam tshuam .

Hauv vitro liraglutide qhia txog lub peev txheej qis rau lub pharmacokinetics ntawm lwm cov tshuaj muaj zog, hloov pauv uas cuam tshuam nrog cytochrome ₄₅₀ ntxiv rau kev khi rau cov protein plasma.

Liraglutide ua rau qeeb me ntsis hauv lub plab zom mov, tuaj yeem cuam tshuam qhov nqus ntawm cov tshuaj uas siv ib txhij sab hauv.

Liraglutide tsis pauv pauv tag nrho cov tshuaj paracetamol tom qab siv ib zaug xwb ntawm 1000 mg. Qhov siab tshaj plaws ntawm paracetamol (C _max ) txo los ntawm 31%, thiab lub sijhawm los mus txog qhov siab tshaj (t _max ) nce rau 15 feeb. Nrog rau kev siv paracetamol thooj txhij, kev hloov kho tshuaj tsis tas yuav tsum tau.

Atorvastatin Liraglutide tsis pauv pauv qhov tag nrho cov tshuaj tiv thaiv ntawm atorvastatin ntawm thaj chaw tseem ceeb hauv chaw kho mob tom qab ib koob tshuaj nws ntawm ib koob ntawm 40 mg. Hauv qhov no, nrog kev siv tib lub sijhawm Viktozoy® kev hloov kho ntawm atorvastatin tsis xav tau. Cov neeg ua haujlwm nrog liraglutide C _max atorvastatin txo tsawg dua 38%, thiab t _max nce txij 1:00 txog 3:00.

Griseofulvin Liraglutide tsis hloov pauv qhov tag nrho ntawm griseofulvin tom qab ib koob tshuaj 500 mg. C _max nce los ntawm 37%, thaum t _max tsis hloov. Koob kev hloov kho thaum siv griseofulvin thiab lwm yam qis hauv paus nrog qhov siab permeability tsis tas yuav.

Lisinopril thiab digoxin

Tom qab txhaj ib zaug ntawm 20 mg ntawm lisinopril lossis 1 mg ntawm digoxin hauv kev sib xyaw nrog liraglutide, qhov kev txo qis hauv thaj chaw hauv qab qhov xav txog lub sijhawm (AUC) nkhaus ntawm cov tshuaj no tau sau tseg los ntawm 15% thiab 16%, feem, nrog C _max txo los ntawm 27% thiab 31%, feem. T _max lisinopril nce txij 6:00 txog 8:00, thaum digoxin nce ntxiv los ntawm 1:00 txog 1.5 teev. Raws li cov txiaj ntsig no, thaum siv liraglutide, kev kho tshuaj lisinopril lossis digoxin yog tsis xav tau.

Nrog rau kev siv tib rab koob ntawm kev tiv thaiv qhov ncauj, liraglutide txo C _max ethinyl estradiol lossis levonorgestrel los ntawm 12% thiab 13%, thiab, t _max nce los ntawm 1.5 teev. Qhov no tsis tau ua rau pom kev cuam tshuam hauv kev saib xyuas rau txhua qhov kev cuam tshuam ntawm ethinyl estradiol lossis levonorgestrel, uas qhia tias kev coj ua ke ntawm liraglutide yuav tsis cuam tshuam nrog kev tiv thaiv zoo ntawm ethinyl estradiol thiab levonorgestrel.

Warfarin thiab lwm yam tshuaj txuas rau kev txij nkawm

Tsis muaj kev tshawb fawb txog kev sib txuas yeeb tshuaj. Thaum pib ntawm kev kho mob nrog Viktoza® rau cov neeg mob uas tau txais warfarin lossis lwm yam kev coj ua txij nkawm, kev saib xyuas ntau zaus ntawm INR (Kev Ntsuas Cov Neeg Txom Nyem Tebchaws Thoob Ntiaj Teb) tau pom zoo.

Hauv cov neeg mob uas muaj hom mob ntshav qab zib hom 2 mob ntshav qab zib mellitus nrog kev tswj hwm ntawm insulin, sib xyaw ua ke (5 U / kg) thiab liraglutide (1.8 mg) pom tias tsis muaj kev cuam tshuam ntawm kev sib txuam pharmacokinetic thiab pharmacodynamic.

Cov Tshuaj Pharmacokinetics

Tom qab ua haujlwm subcutaneous, liraglutide nqus tau qeeb, T_max (lub sijhawm kom mus txog qhov siab tshaj plaws) hauv cov ntshav yog 8-12 teev. C_max (qhov siab tshaj plaws) hauv cov ntshav tom qab kev tswj hwm ib koob ntawm 0.6 mg yog 9.4 nmol / L. Thaum siv cov koob tshuaj ntawm 1.8 mg nruab nrab C_ss (ua kom siab sib npaug) hauv ntshav mus txog li 34 nmol / L. Cov kis ntawm cov tshuaj tau txhim kho hauv qhov sib piv nrog cov koob tshuaj. Kev nkag siab ntawm tus kheej coefficient ntawm kev sib txawv rau AUC (thaj chaw hauv qab qhov ntsuas-lub sijhawm nkhaus) tom qab tswj hwm ntawm liraglutide hauv ib qho tshuaj yog 11%. Kev tsis raug cai ntawm bioavailability yog li 55%.

Xauj V_d (ntim ntawm kev faib khoom) ntawm liraglutide hauv cov ntaub so ntswg nrog subcutaneous txoj kev tswj hwm yog 11-17 u, tus nqi nruab nrab ntawm V_d tom qab kev tswj hwm zoo - 0.07 l / kg. Cov ntsiab lus tseem ceeb ntawm liraglutide nrog cov plasma protein yog sau tseg (> 98%).

Kev siv cov metabolism hauv liraglutide tshwm sim zoo li cov protein loj, tsis tau koom ua ib txoj hauv kev rau kev nthuav tawm ntawm qee yam khoom hauv nruab nrog cev. Rau 24 teev tom qab kev tswj hwm ntawm tib qho tshuaj, cov tshuaj tsis hloov pauv tseem ua lub ntsiab lus tseem ceeb ntawm cov ntshav muaj ntshav. Ob lub cev tshuaj tau kuaj pom hauv cov ntshav (≤ 9 thiab ≤ 5% ntawm tag nrho cov koob tshuaj).

Tsis hloov pauv liraglutide tom qab muab tshuaj 3 H-liraglutide tso zis lossis tso quav tsis tau txiav txim. Tsuas yog ib feem me me ntawm cov metabolites cuam tshuam nrog cov tshuaj tau tawm ntawm lub raum los yog los ntawm cov hnyuv (6 thiab 5%, feem). Tom qab subcutaneous thawj coj ntawm ib koob tshuaj liraglutide, qhov nruab nrab ntawm kev txiav tawm hauv lub cev yog kwv yees li 1.2 l / h nrog kev tshem tawm T_1/2 txog 13 teev.

Daim ntawv tso tawm thiab ntim khoom

3 ml ntawm cov tshuaj hauv daim cartridge ntawm iav 1 hydrolytic chav kawm, corked nrog lub disk ntawm bromobutyl roj hmab / polyisoprene ntawm ib sab thiab lub piston ntawm bromobutyl roj hmab ntawm lwm yam. Daim cartridge raug muab ntim rau hauv lub hnab yas uas muaj cov kua roj hmab pov tseg rau ntau qhov kev hno.

2 cov yas yas uas siv tshuaj txav rau ntau cov kev txhaj tshuaj ua ke nrog cov lus qhia rau kev siv kho mob hauv lub xeev thiab lus Lavxias yog muab tso rau hauv pob ntawv los qhia.

Txhua tus xaum xaum hluav taws xob (3 ml) muaj 30 koob ntawm 0.6 mg, 15 koob tshuaj 1.2 mg lossis 10 koob tshuaj 1.8 mg ntawm liraglutide.

Kev ntsuas rau siv

Raws li cov lus qhia, Viktoza siv rau kev mob ntshav qab zib hom 2 nrog rau kev noj haus thiab kev tawm dag zog kom ua tiav glycemic tswj.

Txoj hauv kev ntawm txoj kev siv tshuaj:

tshuaj mob hlwb
kev sib txuas ua ke nrog ib lossis ntau qhov ncauj hypoglycemic tus neeg sawv cev (thiazolidinediones, sulfonylureas, metformin) hauv cov neeg mob uas tsis ua tiav cov glycemic tswj tau zoo nyob rau yav dhau los kho,
kev sib xyaw nrog kev kho mob nrog basal insulin hauv cov neeg mob uas ua tsis tiav ua tiav kev tswj glycemic siv Victoza ua ke nrog metformin.

Cov lus qhia rau kev siv Victoza: txoj kev thiab qhov ntau npaum li cas

Victoza yuav tsum tau muab tshuaj subcutaneously rau hauv lub plab, xub pwg lossis ncej puab ib hnub ib zaug, tsis hais noj mov dab tsi. Qhov chaw thiab lub sijhawm ntawm kev txhaj tshuaj tuaj yeem hloov tau yam tsis muaj kev hloov kho koob tshuaj, txawm li cas los xij, nws yog qhov tsim nyog los tswj cov tshuaj nyob rau tib lub sijhawm ntawm hnub, uas yooj yim rau tus neeg mob.

Txhawm rau txhawm rau txhim kho lub plab zom mov, kev kho mob yog pom zoo nrog koob tshuaj txhua hnub ntawm 0.6 mg. Tom qab ib lub lim tiam tsawg kawg, cov koob tshuaj tau nce siab txog 1.2 mg. Yog tias tsim nyog, txhawm rau kom ua tiav cov kev tswj hwm zoo glycemic, suav nrog qhov kev kuaj mob ntawm Victoza, qhov kev nce ntxiv rau 1.8 mg yog ua tau yam tsawg ib lub lim tiam tom qab. Kev siv cov koob tshuaj ntau dua yog tsis pom zoo.

Cov tshuaj muaj peev xwm ua tau ntxiv rau qhov kev kho mob txuas ntxiv nrog metformin los yog kev sib koom tes kho nrog metformin ua ke nrog thiazolidinedione. Cov koob ntawm cov xim tom kawg tsis tas yuav kho.

Cov neeg mob tuaj yeem ntxiv rau sulfonylurea derivative kev kho mob lossis kev sib txuas ua ke metformin ua ke nrog sulfonylurea derivatives. Hauv qhov no, kom txo qis kev pheej hmoo ntawm kev tsim cov ntshav tsis txaus siab, qhov koob tshuaj sulfonylurea derivatives yuav tsum raug txo kom tsawg.

Victoza tseem tuaj yeem ntxiv rau cov tshuaj insulin basal, tab sis kom txo qis kev pheej hmoo ntawm hypoglycemia, nws yog qhov tsim nyog los txo cov koob tshuaj insulin.

Thaum twg tsis txhaj koob tshuaj:

yog tias tsis pub dhau 12 teev dhau los, koj yuav tsum nkag mus rau qhov tsis nco qab sai li sai tau,
yog tias ntau dua 12 teev tau dhau mus lawm, koob tshuaj yuav tsum muab ntxiv rau hnub tom qab ntawm lub sijhawm teem, i.e., nws tsis tas yuav them nyiaj rau qhov koob tshuaj uas ploj lawm los ntawm kev qhia ntxiv lossis ntxiv rau ob zaug.

Kev taw qhia ntawm kev siv tshuaj

Txhua rab koob xwj yog tsim rau ib leeg siv.

Cov tshuaj yuav tsum tau muab tshuaj siv cov koob siv li 8 hli ntev thiab txog 32G tuab (tsis suav nrog, yog li ntawd yuav nyias siv). Cov koob txhaj tshuaj siv ua ke yog nrog cov koob txhaj tshuaj pov tseg NovoTvist thiab NovoFayn.

Kev tsim txom Victoza yuav tsum tsis txhob siv yog tias cov tshuaj zoo li txawv dua li kua ntshiab, yuav luag tsis muaj kob lossis tsis muaj kob.

Koj tsis tuaj yeem nkag mus rau cov tshuaj yog tias nws tau hla tawm.

Tsis txhob tso xaum xaum nrog cov koob txuas. Tom qab txhua txoj kev txhaj tshuaj, nws yuav tsum tau muab pov tseg. Qhov kev ntsuas no tiv thaiv cov tshuaj ua kom quav, paug thiab kis ntawm cov tshuaj, thiab tseem tuaj yeem lav qhov raug.

Cia rau cov neeg mob

Khaws ntawm 2 ° C rau 8 ° C (hauv tub yees). Tsis khov.

Rau rab koob xaum xaum siv: siv li ntawm 1 hlis. Khaws ntawm qhov kub thiab txias tsis tshaj 30 ° C lossis los ntawm 2 º C txog 8 º C (hauv tub yees). Tsis khov. Tsis txhob tso nrog rab koob txuas nrog. Npog daim ntawv npuav qhwv nrog lub hau los tiv thaiv nws ntawm lub teeb.

Khaws tsis ncav cuag ntawm cov menyuam yaus!

Kev Siv thiab Kev Qhia Tawm Tseg

Lub Victozao tsis tuaj yeem siv yog tias nws zoo txawv dua li kua ntshiab thiab tsis muaj xim lossis yuav luag tsis muaj kua.

Siv tsis tau Victoza® yog tias nws tau khov.

Victoza® tuaj yeem siv tau yog siv cov koob kom txog li 8 mm ntev thiab mus txog 32G tuab. Lub koob txhaj tshuaj yog npaj rau kev siv ua ke nrog NovoFine® lossis NovoTvist® cov rab koob uas siv pov tseg.

Kev hno koob tsis suav nrog hauv pob.

Tus neeg mob yuav tsum ceeb toom tias siv koob yuav tsum tau muab pov tseg tom qab txhua txoj kev txhaj tshuaj, thiab tseem yuav tsum khaws cov cwj mem uas muaj lub koob txhaj tshuaj tso nrog. Xws li kev ntsuas yuav tiv thaiv kev sib kis, kev kis tau thiab txau ntawm cov tshuaj los ntawm cov xaum xoob thiab lav kev noj tshuaj kom yog.