Tus mob ntshav qab zib nrog hom thib ob tuaj yeem tswj tsis tau qab zib tsuas yog kev pab ntawm kev noj zaub mov kom tsawg thiab ua si lub cev. Kev ua haujlwm ntawm tus neeg mob siab rau mob siab dua txhua xyoo. Hauv cov xwm txheej zoo li no, ntsiav tshuaj ntawm vildagliptin, kev tsim tshuaj tshiab hypoglycemic nrog lub tswv yim tshwj xeeb uas tsis txhawb lossis txwv, tab sis rov kho txoj kev sib raug zoo hauv cov islet nruab nrab ntawm α thiab β hlwb ntawm lub txiav, tuaj yeem pab tau.
Yuav ua li cas siv tau thiab muaj kev nyab xeeb rau kev siv mus sij hawm ntev, thiab qhov chaw twg vildagliptin nyob nrog cov tshuaj sib piv thiab lwm cov tshuaj tiv thaiv kab mob?
Keeb kwm ntawm incretin
Xyoo 1902, nyob rau London, ob lub tsev kawm qib siab physiology cov xibfwb Ernest Starling thiab William Bylize tau pom ib qho tshuaj nyob rau hauv plab hnyuv plab ntawm tus npua uas txhawb nqa lub txiav. 3 xyoos tau dhau los ntawm kev tshawb pom paub daws teeb rau qhov nws siv. Xyoo 1905, Dr. Benjamin Ntau dua los ntawm Liverpool tau muab tus neeg mob ntshav qab zib hom 2 nrog rau cov kua xoos ntawm tus npua duodenum 14 g peb zaug ib hnub. Hauv thawj lub hlis ntawm kev kho mob, qab zib hauv cov zis tau poob ntawm 200 g mus rau 28 g, thiab tom qab 4 lub hlis nws tsis tau txiav txim siab txhua lub sijhawm hauv kev tshuaj ntsuam, thiab tus neeg mob rov qab mus ua haujlwm.
Lub tswv yim tsis tau txais kev txhim kho ntxiv, vim hais tias lub sijhawm ntawd muaj ntau lub tswv yim sib txawv txog kev kho tus mob ntshav qab zib li cas, tab sis txhua yam tau dhau los ntawm kev pom ntawm insulin hauv 1921, uas tau ntev los hla tawm txhua qhov kev tsim tawm. Kev tshawb fawb ntawm cov tshuaj incretin (lub npe hu ua tshuaj sib cais los ntawm hnoos qeev nyob rau sab qaum kev ntawm cov plab hnyuv taum) tau txuas ntxiv tsuas yog tom qab 30 xyoo.
Xyoo 60 ntawm lub xyoo pua xeem, cov xibfwb M. Perley thiab H. Elric qhia txog qhov ua kom muaj zog: muaj cov tshuaj insulin ntau ntxiv nyob rau tom qab ntawm lub qhov ncauj cov ntshav qab zib ua piv nrog cov leeg ntshav.
Hauv xyoo 70, tau muaj cov kua nplaum-tiv thaiv insulinotropic polypeptide (HIP), uas lub plab hnyuv phab ntsa ua haujlwm zoo. Nws lub luag haujlwm yog txhawm rau txhim kho lub biosynthesis thiab kua-tso lub tso pa tawm ntawm cov kua dej, nrog rau hepatic lipogenesis, nqaij thiab adipose cov nqaij, ua kom loj hlob ntawm P-hlwb, nce lawv cov rhiab rau apoptosis.
Hauv xyoo 80, cov kev tshaj tawm tau tshwm sim rau kev kawm ntawm hom 1 glucagon-zoo li peptide (GLP-1), uas L hlwb hluavtaws los ntawm proglucagon. Nws kuj tseem muaj cov tshuaj insulinotropic thiab. Tus xibfwb G. Tswb tau tawm qauv nws cov qauv thiab tau hais txog lub luag haujlwm tshiab rau kev tshawb nrhiav kev kho mob ntshav qab zib (piv rau cov tshuaj metformin thiab sulfanylurea npaj).
Lub caij nyoog ntawm incretins nce nyob rau hauv 2000, thaum lub ntiaj teb kawg tsis tau ua dua, thiab thawj cov lus tau tshaj tawm rau ntawm Asmeskas Lub Rooj Sab Laj uas tus xibfwb Rottenberg tau qhia tias qee yam khoom siv DPP 728 muaj zog, tsis hais txog kev noj zaub mov noj, tiv thaiv DPP-4 hauv tib neeg.
Tus tsim ntawm thawj inhibitor ntawm DPP 728 (vildagliptin) yog Edwin Willhauer, ib tug neeg ua haujlwm ntawm kev tshawb fawb ntawm lub tuam txhab Swiss Novartis.
Cov molecule yog qhov txaus siab nyob rau hauv tias nws khi kom meej meej dhau los ntawm oxygen mus rau amino acid lub luag haujlwm rau catalytic kev ua si ntawm DPP-4 tib neeg enzyme.
Cov tshuaj tau txais nws lub npe los ntawm thawj peb tus tsiaj ntawv ntawm nws lub xeem - VIL, YOG - Dipeptidyl Amine Peptidase, GLI - cov lus tseem ceeb uas WHO siv rau cov tshuaj tiv thaiv kab mob, TIN - cov lus tseem ceeb hais txog qhov tshuaj tiv thaiv enzyme.
Kev ua tiav tuaj yeem suav hais tias yog kev ua haujlwm ntawm cov xibfwb E. Bossi, nyob rau hauv uas nws tau sib cav tias kev siv vildagliptin nrog metformin txo tus nqi glycosylated hemoglobin ntau dua 1%. Ntxiv rau qhov ua rau txo qis qab zib, cov tshuaj muaj lwm txoj kev tuaj yeem:
- Txo cov ntxim nyiam ntawm lub qog ntshav ntshav los ntawm 14 zaug, thaum piv nrog kev sib txuas ntawm sulfonylurea (PSM);
- Nrog txoj kev kho mob ntev ntev, tus neeg mob tsis hnyav;
- Txhim kho β-cell muaj nuj nqi.
Tsis zoo li Asmeskas cov txheej txheem algorithm uas tso vildagliptin rau ntawm kab thib 2 ntawm cov tshuaj qab zib-txo cov tshuaj, Lavxias cov kws kho mob tso ntaug ntawm 1-2-3 qhov chaw thaum xaiv cov tshuaj hypoglycemic, txawm tias qhov tseeb tias pheej yig tshaj plaws hnub no yog sulfanilurea npaj.
Vildagriptin (cov tshuaj muaj npe lag luam yog Galvus) tau tshwm sim rau ntawm kev lag luam tshuaj Lavxias xyoo 2009.
Cov kws tshawb fawb Lavxias tau xaus rau qhov xaus tias nws yog qhov yuav tsum tau xaiv los ua ke ntawm normalizing glycemia nrog Galvus ua ke nrog ntau hom tshuaj uas cuam tshuam rau ntau yam txheej txheem ntawm kev txhim kho tus kabmob (tshuaj tua kabmob tsis txaus, kev tsim tawm insulin, glucagon synthesis). Thaum pib, thaum glycosylated hemoglobin twb tau ntau dua 9%, nyob rau hauv qhov tsis muaj cov lus hais ntawm kev kho mob ntawm decompensation lossis nrog kev ua kom muaj zog ntawm kev kho mob kiag, kev sib xyaw ntawm 2-4 tshuaj yog ua tau.
Pharmacological Nta ntawm Vildagliptinum
Vildagliptin (hauv daim ntawv qhia, hauv Latin, Vildagliptinum) yog tus sawv cev ntawm chav kawm ntawm cov tshuaj hypoglycemic tsim los txhawb cov islets ntawm Langerhans thiab xaiv tau inhibit dipeptidyl peptidase-4. Qhov enzyme no muaj qhov ua rau lub ntsej muag zoo li glucagon-zoo li hom 1 peptide (GLP-1) thiab glucose-dependant insulinotropic polypeptide (HIP) (ntau dua 90%). Txo nws cov haujlwm, incretin ua kom nrawm nrawm nyas ntawm GLP-1 thiab HIP los ntawm cov hnyuv mus rau cov hlab ntshav thaum nruab hnub. Yog tias cov peptide cov ntsiab lus nyob ze rau qhov ib txwm nyob, β-hlwb muaj qhov ua rau cov piam thaj ntau dua, thiab insulin ntau lawm. Qhov ntsuas ntawm kev ua of-hlwb tau ncaj qha mus rau lawv qhov kev nyab xeeb. Qhov no txhais tau hais tias nyob rau hauv cov neeg mob ntshav tsis zoo, kev siv vildagliptin yuav tsis cuam tshuam rau cov lus sib txuas ntawm cov tshuaj insulin thiab cov glucometer. Ib koob tshuaj ntawm 50-100 mg / hnub rau cov neeg mob ntshav qab zib. muab kev nce siab tsis tu ncua hauv kev ua haujlwm ntawm β-hlwb.
Tsis tas li ntawd, thaum cov tshuaj txhawb qhov ua haujlwm ntawm GLP-1 peptide, cov kua nplaum ua haujlwm tseem nce ntxiv hauv α-cov cell uas neutralize cov nyhuv ntawm glucagon. Hyperglucagonemia ua lub luag haujlwm tseem ceeb hauv kev txhim kho cov txheej txheem tom qab pathological. Qhov peculiarity ntawm cov tshuaj yog tias nws tsis tsuas yog txhawb cov txheej txheem, nws rov qab ua haujlwm ntawm α thiab. Hlwb. Qhov no tshaj tawm tsis tsuas yog nws cov txiaj ntsig, tab sis kuj muaj kev nyab xeeb nrog kev siv lub sijhawm ntev.
Los ntawm nce cov ntsiab lus ntawm GLP-1, vildagliptin ua rau kev nkag siab zoo ntawm α-hlwb rau cov kua nplaum. Qhov no pab tswj cov khoom ntawm glucagon, txo nws thaum lub sijhawm noj mov yuav txo tau cov tshuaj insulin.
Kev nce ntxiv ntawm cov insulin / glucagon piv nrog hyperglycemia tawm tsam keeb kwm ntawm lub ntsiab lus siab ntawm GLP-1 thiab HIP provokes txo qis rau daim siab glycogen zais cia txhua lub sijhawm, tsis hais txog kev noj zaub mov.
Tag nrho cov yam ua rau muaj kev tswj ruaj khov glycemic.
Ib qho ntxiv ntxiv yuav tau txhim kho lipid metabolism, txawm hais tias tsis muaj qhov sib txuas ncaj qha ntawm cov nyhuv ntawm peptides thiab β-hlwb hauv cov teeb meem no.
Hauv qee cov tshuaj, nrog kev nce hauv cov ntsiab lus ntawm GLP ntawm hom 1, kev khiav tawm ntawm cov ncauj lus qeeb, tab sis nrog kev siv vildagliptin, tsis muaj cov cim zoo sib xws.
Kev nthuav dav thiab ntev lub sij hawm ntawm incretin tau nqa tawm hauv ntau lub teb chaws. Thaum Galvus tau noj, 5795 cov neeg mob ntshav qab zib nrog hom 2 tus neeg uas coj cov tshuaj hauv nws daim ntawv dawb huv lossis hauv kev sib xyaw nrog hypoglycemic cov neeg sawv cev tau sau ib qho kev poob qis hauv cov piam thaj thiab glycosylated hemoglobin.
Pharmacokinetics ntawm vildagliptin
Lub bioavailability ntawm cov tshuaj yog 85%, tom qab lub qhov ncauj tswj hwm nws yog nqus sai. Tom qab noj cov tshuaj ua ntej noj mov, qhov siab tshaj plaws ntawm cov tshuaj tiv thaiv metabolite pom tom qab 1 teev. 45 feeb Yog tias koj noj cov tshuaj nrog zaub mov noj, qhov nqus ntawm qhov tshuaj raug txo los ntawm 19%, thiab lub sijhawm ncav cuag nws yog nce li 45 feeb. Lub inhibitor tsis muaj zog khi rau cov protein - tsuas yog 9%. Nrog txoj kev nqus ntshav, qhov ntim ntawm kev faib tawm yog 71 litres.
Txoj hauv kev tseem ceeb ntawm kev nthuav tawm ntawm cov khoom siv metabolite yog biotransformation, nws tsis yog metabolized los ntawm cytochrome P450, tsis yog qhov tsim tawm, thiab tsis txwv cov isoenzymes. Yog li ntawd, muaj peev xwm cuam tshuam txog kev sib txuam yeeb tshuaj hauv incretin yog tsawg.
Galvus tso tawm daim ntawv
Lub tuam txhab Swiss Novartis Pharma tsim Galvus hauv cov ntsiav tshuaj hnyav 50 mg. Hauv cov khw muag tshuaj, koj tuaj yeem pom ob hom tshuaj raws vildagliptin. Hauv ib kis, vildagliptin ua raws li cov tshuaj nquag, hauv lwm qhov - metformin. Cov Ntawv Tso Tawm:
- "Pure" vildagliptin - 28 tab. 50 mg txhua;
- Vildagliptin + metformin - 30 tab. 50/500, 50/850, 50/1000 mg txhua tus.
Kev xaiv ntawm kev noj tshuaj thiab kev tswj hwm tshuaj yog qhov muaj peev xwm ntawm tus endocrinologist. Rau vildagliptin, cov lus qhia rau kev siv muaj cov npe kwv yees ntawm cov koob tshuaj txheem. Incretin yog siv rau kev kho mob monotherapy lossis hauv ib txoj hauv kev nyuaj (nrog insulin, metformin thiab lwm yam tshuaj tua kab mob). Qhov koob tshuaj rau txhua hnub yog 50-100 mg.
Yog tias Galvus raug muab nrog sulfonylureas, ib koob tshuaj ib hnub yog 50 mg. Nrog rau kev teem sij hawm 1 ntsiav tshuaj, nws yog qaug cawv thaum sawv ntxov, yog tias ob, tom qab ntawv sawv ntxov thiab yav tsaus ntuj.
Nrog rau kev sib xyaw ua ke vildagliptin + metformin + sulfonylurea derivatives, tus qauv niaj hnub tus nqi nce mus txog 100 mg.
Lub hauv paus tseem ceeb ntawm kev siv tshuaj hauv lub raum yog dhau los ua ib qho kev ua kom tsis haum rau lub cev;
Muab cov khoom siv kho mob xub ntiag uas muaj tshuaj tso rau hauv qhov chaw ncav cuag rau me nyuam yaus mloog. Cov chaw tswj kub kub - txog 30 ° С, txee lub neej - txog 3 xyoos. Nws yog qhov txaus ntshai rau noj cov tshuaj uas tas sij hawm, txij li thaum lawv cov hauj lwm raug txo, thiab qhov ntxim nyiam ntawm cov kev mob tshwm sim yog nce.
Kev taw qhia rau kev siv cov incretin
Cov tshuaj, uas nws ua raws li qhov ua kom tau txiaj ntsig, tsim nyog ntawm kev sib tw nrog metformin thiab derivatives ntawm sulfanylurea. Nws tau tsim los kho cov neeg mob uas muaj ntshav qab zib hom 2 ntawm txhua ntu mob.
Cov kev sib txuam tsis haum thiab qhov xav tsis tau
Vildagliptin yuav zam tau yooj yim los ntawm cov neeg mob ntshav qab zib dua li lwm cov tshuaj tiv thaiv hypoglycemic. Ntawm cov contraindications:
Cov neeg galactose tsis kam;- Lactose tsis txaus;
- Kev ua haujlwm tsis haum rau cov tshuaj xyaw ntawm cov mis mos;
- Cov piam thaj-galactose malabsorption.
Cov neeg galactose tsis kam;Tsis muaj ntaub ntawv txaus ntseeg txog cov txiaj ntsig ntawm incretin rau tus mob ntshav qab zib rau menyuam yaus, cev xeeb tub thiab lactating leej niam, yog li ntawd, ib qho tshuaj metabolite tsis tau sau tseg rau cov neeg mob ntawd.
Thaum siv Galvus hauv ib txoj kev xaiv kho, cov kev mob tshwm sim tau sau cia:
- Nrog rau txoj kev kho mob ntshav qab zib - hypoglycemia, poob kev sib koom tes, mob taub hau, o, hloov pauv ntawm kev tso quav;
- Vildagliptin nrog Metformin - kev sib zog txhais tes thiab cov tsos mob zoo sib xws rau yav dhau los;
- Vildagliptin nrog sulfonylurea derivatives - asthenia (kev puas hlwb) ntxiv rau daim ntawv dhau los;
- Vildagliptin nrog thiazolidinedione derivatives - ntxiv rau cov qauv ua qauv, ib qho kev nce hauv lub cev hnyav yog qhov ua tau;
- Vildagliptin thiab insulin (qee zaum nrog metformin) - mob dyspeptic, hypoglycemia, mob taub hau.
Hauv qee tus neeg mob, kev tsis txaus siab ntawm urticaria, tev ntawm daim tawv nqaij thiab qhov pom ntawm cov hlwv, exacerbation ntawm pancreatitis tau sau tseg. Txawm hais tias daim ntawv teev npe qhov tseem ceeb ntawm qhov tsis xav tau, qhov ntxim li yuav muaj tsawg. Feem ntau cov feem ntau, cov kev ua txhaum ntawm ib ntus xwm yeem thiab kev txiav tawm ntawm cov tshuaj tsis tas yuav.
Cov yam ntxwv ntawm kev kho mob nrog vildagrippin
Tshaj li 15 lub xyoos dhau los, 135 cov kev tshawb fawb txog kev nce qib hauv kev nce qib hauv cov tebchaws txawv. Dab tsi theem ntawm hypoglycemic txoj kev kho mob ntshav qab zib hom 2 yog nws kho?
- Thaum pib, thaum noj hauv "daim ntawv ntshiab";
- Thaum pib ua ke nrog metformin;
- Thaum ntxiv rau metformin los txhim kho nws lub peev xwm;
- Hauv zaj triple: vildagliptin + metformin + PSM;
- Thaum muab sib xyaw nrog basal insulin.
Hauv txhua qhov xwm txheej no, koj tuaj yeem siv vildagliptin. Kev noj tshuaj ntawm 200 mg / hnub yog assimilated yam tsis muaj teeb meem.Txhua lwm yam, kev siv ntau tshaj yog ua tau.
- Yog tias koj noj ib koob tshuaj 400 mg, myalgia, o, kub ib ce, loog ntawm qhov kawg tshwm, qib ntawm lipase nce.
- Hauv koob tshuaj ntawm 600 mg, ceg txhais ceg o, cov ntsiab lus ntawm C-reactive protein, ALT, CPK, myoglobin nce. Ib daim siab kuaj mob yog yuav tsum tau ua, yog tias kev ua haujlwm ntawm ALT lossis AST tshaj li qhov ntsuas dhau los 3 zaug, qhov tshuaj yuav tsum tau hloov.
- Yog tias muaj kab mob siab (piv txwv li daj), yuav tsum tau tshawb pom, cov tshuaj yuav tsum nres kom txog thaum txhua daim siab ua haujlwm tshem tawm.
- Thaum insulin-hom mob ntshav qab zib hom 2 mob ntshav qab zib, vildagliptin tsuas yog ua tau ua ke nrog cov tshuaj hormones.
- Tsis txhob siv tshuaj rau cov ntshav qab zib hom 1, zoo li nyob hauv lub xeev ketoacidosis.
Cov kev tshawb fawb ntawm cov nyhuv ntawm incretin ntawm kev tsom xam tsis tau ua.
Yog tias kev noj tshuaj nrog nrog kev ua txhaum ntawm kev sib koom tes, koj yuav tsum tsis kam tsav tsheb thauj khoom thiab cov txheej txheem nyuaj.
Galvus's analogs thiab nws cov khoom muaj
Ntawm cov tshuaj tiv thaiv analogues, vildagrippin muaj cov tshuaj nrog lwm tus muaj txiaj ntsig hauv lub hauv paus thiab muaj cov txiaj ntsig zoo sib xws.
- Onglisa yog lub tshuaj lom nyob hauv saxagliptin. Nqe - los ntawm 1900 rubles;
- Trazhenta - cov tshuaj ua kom nquag plias linagliptin. Tus nqi nruab nrab yog 1750 rubles;
- Januvia yog cov tshuaj nquag ntawm sitagliptin. Nqe - los ntawm 1670 rubles.
Cov chaw tsim khoom ntawm Novartis Pharma nyob rau hauv Basel (Switzerland), yog li rau vildaglippin tus nqi yuav ua tau raws li European zoo, tab sis tawm tsam keeb kwm yav dhau los ntawm tus nqi ntawm analogues nws zoo li pheej yig. Qhov nruab nrab cov neeg mob ntshav qab zib muaj peev xwm yuav 28 ntsiav tshuaj ntawm 50 mg rau 750-880 rubles.
Professor S.A. Dogadin, Tus Thawj Endocrinologist ntawm Krasnoyarsk Territory, suav tias nws yog qhov tseem ceeb uas cov neeg mob tau txais ntau dua li cov thev naus laus zis tshiab thiab muaj peev xwm kho tau vildagliptin dawb. Peb tos kom nws los nyob hauv tsoomfwv cov nyiam ua cov npe. Txog rau hnub tim, cov yeeb tshuaj no suav nrog hauv cov npe hauv plaub thaj tsam ntawm Lavxias teb sab chaw thiab thaj chaw ntawm muab cov neeg mob ntshav qab zib rau cov lus pom zoo yog nthuav dav.
Professor Yu.Sh. Halimov, Tus Thawj Kws Kho Mob-Endocrinologist ntawm St. Petersburg, sau tseg tias vildagliptin muaj kev ntseeg siab hauv kev ua yeeb yam solo, zoo meej hauv duet, yuav tsis yog superfluous hauv trio. Incretin yog cov twj paj nruag thoob ntiaj teb hauv kev tsim kho cov tshuaj tua kab mob, uas muaj peev xwm ntau nyob hauv nthwv dej ntawm tus neeg xyuas pib lo txawm los ntawm tus kws kho mob uas tsis paub dhau los.
