Vildagliptin - malangizo, ntchito, zithunzi

Anthu odwala matenda ashuga omwe ali ndi mtundu wachiwiri wa matendawa sangathe kuwongolera shuga mothandizidwa ndi zakudya zama carb ochepa komanso kuchita masewera olimbitsa thupi. Magwiridwe a kapamba amayamba kuvuta chaka chilichonse. Zikatero, mapiritsi a vildagliptin, mankhwala achilendo a hypoglycemic omwe ali ndi makina ena apadera omwe samalimbikitsa kapena kuletsa, koma abwezeretsanso ubale womwe uli mkati mwa kanyumba pakati pa maselo a α ndi β a kapamba, angathandize.

Kodi ndizothandiza bwanji kwa nthawi yayitali, ndipo kodi vildagliptin imakhala malo ati pakati pa odziwika bwino ndi othandizira odwala matenda ashuga?

Mbiri ya incretin

Mu 1902, ku London, aprofesa awiri azakuyunivesite a Ernest Starling ndi a William Bylize adapeza chinthu chomwe chimayambitsa matumbo a nkhumba. Zaka zitatu zadutsa kuchokera pakuzindikira zomwe zidakwaniritsidwa mpaka kukwaniritsidwa kwake komwe. Mu 1905, Dr. Benjamin More wochokera ku Liverpool adasankha wodwala wa mtundu wa 2 wodwala kuti amupatse zotupa za duodenum 14 g katatu patsiku. M'mwezi woyamba wa chithandizo chotere, shuga mumkodzo adatsika kuchokera ku 200 g mpaka 28 g, ndipo patatha miyezi inayi sizinatsimikizidwe konse pazowunikira, ndipo wodwalayo amabwerera kuntchito.

Lingaliroli silinapezeke kupitanso patsogolo, chifukwa nthawi imeneyo panali malingaliro osiyanasiyana amomwe amathandizira odwala matenda ashuga, koma zonse zidaphimbidwa ndi kupezeka kwa insulin mu 1921, yomwe kwa nthawi yayitali idakwaniritsa zochitika zonse. Kafukufuku wokhudza impretin (zomwe zimadziwika kuti zimachokera ku ntchofu kumtunda kwa matumbo a chimbudzi) zidapitilizidwa kokha zaka 30.

Mu 60s ya zaka zapitazi, mapulofesa a M. Perley ndi H. Elric adawulula zotsatira za insretin: kuchuluka kwa kupanga kwa insulin pazomwe zimayamwa shuga wa pakamwa poyerekeza ndi kulowetsedwa kwamkati.

Mu 70s, kudwala-insulinotropic polypeptide (HIP) ya glucose, yomwe makoma amkati amatengera. Ntchito zake ndikupititsa patsogolo kukonzekera kwa insulin, komanso kupuma kwa glucose, komanso hepatic lipogenesis, minofu ndi minyewa ya adipose, kuchuluka kwa maselo a P, kukulitsa chidwi chawo cha apoptosis.

Mu 80s, zofalitsa zidawonekera pa kafukufuku wa mtundu wa 1 glucagon-peptide (GLP-1), omwe maselo a L amapanga kuchokera ku prolucagon. Ilinso ndi insulinotropic ntchito. Pulofesa G. Bell adalemba momwe adapangidwira ndikufotokozera njira yatsopano yosakira njira zamatenda a shuga (poyerekeza ndi metformin komanso kukonzekera kwa sulfanylurea).

Kutuluka kwa dzuwa kwa nthawi ya ma incretin kugwera pa 2000, pomwe mathedwe a dziko sanachitike, ndipo uthenga woyamba udaperekedwa ku US Congress momwe Pulofesa Rottenberg adawonetsera kuti chinthu china DPP 728 mwakutayikira, mosasamala kanthu za chakudya, chimaletsa anthu DPP-4.

Wopanga inhibitor woyamba wa DPP 728 (vildagliptin) anali Edwin Willhauer, wogwira ntchito ku labotale yasayansi yaku kampani yaku Swiss Novartis.

Molekyuluyo ndi yosangalatsa chifukwa imagwirizanitsa momveka bwino kudzera mu okosijeni kupita ku amino acid omwe amachititsa zochitika zamphamvu za anthu a DPP-4.

Katunduyu adapeza dzina kuchokera ku zilembo zitatu zoyambirira za mayina awo - VIL, YES - Dipeptidyl Amine Peptidase, GLI - chokwanira chomwe WHO chimagwiritsa ntchito mankhwala othandizira matenda a shuga, TIN - chokwanira chotanthauza enhibme inhibitor.

Kupezaku kungathenso kuonedwa ngati ntchito ya Pulofesa E. Bossi, pomwe akuti kugwiritsa ntchito vildagliptin limodzi ndi metformin kumachepetsa kuchuluka kwa hemoglobin ya glycosylated ndi 1%. Kuphatikiza pa kuchepetsa kwambiri shuga, mankhwalawa ali ndi mwayi wina:

• Imachepetsa mwayi wa hypoglycemia nthawi 14, poyerekeza ndi zotumphukira za sulfonylurea (PSM);
• Ndi chithandizo chautali, wodwalayo sawonda;
• Amasintha ntchito ya β-cell.

Mosiyana ndi ma algorithms aku America omwe amaika vildagliptin pamzere wachiwiri wa mankhwala ochepetsa shuga, madokotala aku Russia amaika ma insretins m'malo a 1-2-3 posankha mankhwala a hypoglycemic, ngakhale atakhala kuti angakwanitse kwambiri masiku ano ndi sulfonylureas.

Vildagriptin (dzina la mankhwalawo ndi Galvus) adapezeka pamsika wazaka za Russia ku 2009.

Asayansi aku Russia adazindikira kuti ndikofunikira kusankha mitundu yosiyanasiyana ya matenda a glycemia ndi Galvus kuphatikiza mitundu ingapo ya mankhwala omwe amakhudza njira zosiyanasiyana za chitukuko cha matendawa (kupatsirana kwa mahomoni, kupanga insulini, kaphatikizidwe ka glucagon). Poyambirira, pamene glycosylated hemoglobin ali kale zoposa 9%, pakalibe kutchulidwa matendawa chifukwa cha kuwonongeka kapena kukula kwa njira yothandizira mankhwalawa, kuphatikiza kwa mankhwalawa kwa mankhwala a 2-4 ndikotheka.

Makhalidwe a Pharmacological a Vildagliptinum

Vildagliptin (mu Chinsinsi, mu Chilatini, Vildagliptinum) ndi woimira gulu la mankhwala oopsa a hypoglycemic omwe amapangitsidwa kuti akalimbikitse zisumbu za Langerhans komanso kusankha zoletsa dipeptidyl peptidase-4. Enzyme iyi imakhumudwitsa mtundu wa glucagon ngati mtundu 1 peptide (GLP-1) ndi glucose wodalira insulinotropic polypeptide (HIP) (oposa 90%). Kuchepetsa ntchito yake, incretin imathandizira kupanga GLP-1 ndi HIP kuchokera m'matumbo kupita m'magazi masana. Ngati zomwe peptide zili pafupi ndizabwinobwino, maselo a β-cell amatha kugwidwa ndi glucose, ndikupanga insulin. Kuchuluka kwa zochitika za β-cell ndizofanana mwachindunji ndi chitetezo chawo. Izi zikutanthauza kuti mu nondiabetesics, kugwiritsa ntchito vildagliptin sikukhudza kapangidwe ka insulin ndi glucometer. Mlingo wa 50-100 mg / tsiku la odwala matenda ashuga. imapereka chiwonjezero chokhazikika pakuwoneka bwino kwa ma β-cell.

Kuphatikiza apo, pamene mankhwalawa amathandizira kupanga GLP-1 peptide, chiwopsezo cha glucose chimakulanso m'magulu a α-cell omwe amalepheretsa mphamvu ya glucagon. Hyperglucagonemia imachita mbali yofunika kwambiri pakukula kwa njira zotsatirazi zamatsenga. Chachilendo cha mankhwalawa ndikuti sichimangoyambitsa zochitika, chimabwezeretsa magwiridwe antchito a maselo a α ndi β. Izi zimatsimikizira osati kugwira ntchito kwake, komanso chitetezo chogwiritsa ntchito nthawi yayitali.

Powonjezera zomwe zili mu GLP-1, vildagliptin imakulitsa chidwi cha α-cell ku glucose. Izi zimathandiza kuwongolera kupanga glucagon, kuichepetsa pakudya kumachepetsa insulin.

Kuwonjezeka kwa kuchuluka kwa insulin / glucagon ndi hyperglycemia motsutsana ndi kumbuyo kwa zinthu zambiri za GLP-1 ndi GUI kumayambitsa kuchepetsedwa kwa secretion ya chiwindi glycogen nthawi iliyonse, mosasamala kanthu za kudya.

Zinthu zonsezi zimapereka chiwongolero chokhazikika cha glycemic.

Kuphatikizanso kwina kudzakhala kutukuka kwa lipid metabolism, ngakhale palibe kulumikizana mwachindunji pakati pazomwe zimachitika peptides ndi β-cell pankhaniyi.

Mankhwala ena, ndikuwonjezeka kwa zomwe zili mu GLP zamtundu 1, kutulutsa kwamkatimu kumachepa, koma pogwiritsa ntchito vildagliptin, palibe mawonetsedwe omwewo.

Kafukufuku owonjezera komanso wautali wa incretin wachitika m'mayiko ambiri. Galum atamwa, anthu 5795 odwala matenda ashuga okhala ndi mtundu 2 omwe adamwa mankhwalawo m'njira yoyenera kapena kuphatikiza othandizira a hypoglycemic adalemba kuchepa kwa shuga ndi glycosylated hemoglobin.

Pharmacokinetics of vildagliptin

The bioavailability wa mankhwalawa ndi 85%, pambuyo pakamwa makonzedwe ake mofulumira. Pambuyo kumwa mapiritsi musanadye, pazotheka metabolite yambiri imawonedwa pambuyo pa ola limodzi. Mphindi 45 Ngati mumwa mankhwalawo ndi chakudya, kuyamwa kwa mankhwalawa kumachepetsedwa ndi 19%, ndipo nthawi yoti mufikire imawonjezeka ndi mphindi 45. The inhibitor mofooka amamangirira mapuloteni - 9% okha. Ndi kulowetsedwa kwa mtsempha, voliyumu yogawa ndi malita 71.

Njira yayikulu yotsatsira metabolite ndi biotransfform, siinapangidwe ndi cytochrome P450, sikuti kuyanjana, sikulepheretsa awa isoenzymes. Chifukwa chake, kuthekera kwa kulumikizana kwa mankhwala mu insretin kumakhala kotsika.

Fomu lomasulidwa la Galvus

Kampani yaku Swiss ya Novartis Pharma imatulutsa Galvus m'mapiritsi olemera 50 mg. Patsamba lamankhwala, mutha kuwona mitundu iwiri ya mankhwala yochokera pa vildagliptin. Munthawi ina, vildagliptin imagwira ngati chophatikiza, china - metformin. Kutulutsa Mafomu:

• "Woyera" vildagliptin - 28 tabu. 50 mg aliyense;
• Vildagliptin + metformin - 30 tabu. 50/500, 50/850, 50/1000 mg aliyense.

Kusankha kwa mankhwala ndi regimen ndiko luso la endocrinologist. Kwa vildagliptin, malangizo omwe angagwiritsidwe ntchito ali ndi mndandanda woyenera wa mulingo woyenera. Incretin imagwiritsidwa ntchito ngati monotherapy kapena mawonekedwe osavuta (okhala ndi insulin, metformin ndi mankhwala ena a antidiabetic). Mlingo watsiku ndi tsiku ndi 50-100 mg.

Ngati Galvus adayikidwa ndi sulfonylureas, mlingo umodzi patsiku ndi 50 mg. Ndi piritsi limodzi, aledzera m'mawa, ngati awiri, ndiye m'mawa ndi madzulo.

Ndi regimen vildagliptin + metformin + sulfonylurea zotumphukira, muyezo tsiku lililonse umafikira 100 mg.

Yogwira pophika mankhwala a impso imachotsedwa mu mawonekedwe a metabolite osagwira; kusintha kwa mankhwalawa ndikotheka ndi aimpso.

Ikani zida zogwiritsira ntchito pa malo oyamba osagwirizana ndi ana. Malo osungira kutentha - mpaka 30 ° С, moyo wa alumali - mpaka zaka 3. Ndizowopsa kumwa mankhwala omwe adatha, chifukwa kutha kwake kumachepa, ndipo mwayi wazotsatira zake ukukula.

Zisonyezero zogwiritsira ntchito intretin

Mankhwala, omwe zochita zake zimatengera mphamvu ya incretin, anali woyenera kupikisana ndi metformin komanso zotumphukira za sulfanylurea. Anapangira kuti azithandiza odwala omwe ali ndi matenda a shuga 2 pamtundu uliwonse wa matendawa.

Imathandizanso mu regimen yokhala ndi magawo awiri mukaphatikizidwa ndi metformin, kukonzekera kwa sulfonylurea, insulini ndi thiazolidinedione, ngati chithandizo cham'mbuyomu ndi mankhwalawa sichinapereke zotsatira zomwe mukufuna.

Contraindication ndi zosafunikira zotsatira

Vildagliptin imalekerera mosavuta ndi odwala matenda ashuga kuposa njira zina za hypoglycemic. Mwa zina zotsutsana:

• Munthu galactose tsankho;
• Lactose akusowa;
• Hypersensitivity kwa yogwira pophika zipatso;
• Glucose-galactose malabsorption.

Palibe chodalirika chokhudza zovuta za odwala omwe ali ndi matenda ashuga a ana, amayi oyembekezera komanso oyembekezera, motero, metabolite sinafotokozeredwe magulu amtunduwu a odwala.

Mukamagwiritsa ntchito Galvus njira iliyonse ya chithandizo, mavuto adalembedwa:

• Ndi monotherapy - hypoglycemia, kuchepa kwa mgwirizano, kupweteka kwa mutu, kutupa, kusintha kwa mtundu wa defecation;
• Vildagliptin ndi Metformin - manja akunjenjemera ndi zizindikiro zofananira ndi zam'mbuyomu;
• Vildagliptin yokhala ndi zotumphukira za sulfonylurea - asthenia (matenda amisala) amawonjezeredwa pamndandanda wam'mbuyomu;
• Vildagliptin ndi zotumphukira za thiazolidinedione - kuwonjezera pazizindikiro wamba, kuwonjezeka kwa thupi kumatha;
• Vildagliptin ndi insulin (nthawi zina ndi metformin) - matenda osokoneza bongo, hypoglycemia, mutu.

Mwa odwala ena, madandaulo a urticaria, kupindika kwa khungu ndi mawonekedwe a matuza, kuchuluka kwa kapamba kunalembedwa. Ngakhale kuti pali mndandanda wazotsatira zoyipa, mwayi wopezekapo ndi wochepa. Nthawi zambiri, izi zikuphwanya kwa kanthawi kochepa komanso kusiya mankhwala sikufuna.

Zolemba zamankhwala ndi vildagrippin

Pazaka 15 zapitazi, maphunziro 135 azachipatala a incretin adachitidwa m'maiko osiyanasiyana. Ndi gawo liti la hypoglycemic therapy la mtundu 2 wa shuga lomwe limalembedwa?

• Poyambirira, mukamadyedwa mu mawonekedwe "oyera";
• Kumayambiriro osakanikirana ndi metformin;
• Mukawonjezeredwa ndi metformin kuti muwonjezere mphamvu zake;
• Munjira yapatatu: vildagliptin + metformin + PSM;
• Akaphatikizidwa ndi basulin insulin.

Pazochitika zonsezi, mutha kugwiritsa ntchito vildagliptin. Mlingo wa 200 mg / tsiku umatheka popanda mavuto. Nthawi zina, bongo umatheka.

• Ngati mutenga limodzi lokha la 400 mg, myalgia, kutupa, kutentha thupi, kuchuluka kwa malekezero kumawonekera, mulingo wa lipase ukuwonjezeka.
• Pa mlingo wa 600 mg, miyendo yotupa, zomwe zimakhala ndi mapuloteni a C-reactive, ALT, CPK, myoglobin amayamba. Kuunika kwa chiwindi kumafunikira, ngati ntchito ya ALT kapena AST idaposa nthawi 3 nthawi, mankhwalawo ayenera kusinthidwa.
• Ngati hepatic pathologies (mwachitsanzo, jaundice) amadziwika, mankhwalawa amayimitsidwa mpaka ma pathologies onse a chiwindi atachotsedwa.
• Pankhani ya matenda a shuga a 2 omwe amadalira insulin, vildagliptin ndizotheka pamodzi ndi mahomoni.
• Osagwiritsa ntchito mankhwalawa a matenda a shuga 1, komanso a ketoacidosis.

Kafukufuku wokhudzana ndi mphamvu ya impretin pa concentration sanachitike.

Ngati kumwa mankhwala kumayendera limodzi ndi kuphwanya mgwirizano, muyenera kukana kuyendetsa magalimoto ndi njira zovuta.

Zofananira za Galvus ndi kupezeka kwake

Mwa analogues, vildagrippin ali ndi mankhwala omwe ali ndi chiwalo china chogwira ntchito m'munsi ndi makina ofanana.

1. Onglisa ndi chophatikiza chogwira ntchito mu saxagliptin. Mtengo - kuchokera ku ma ruble a 1900;
2. Trazhenta - yogwira pophika linagliptin. Mtengo wapakati ndi ma ruble 1750;
3. Januvia ndiye chinthu chogwira ntchito cha sitagliptin. Mtengo - kuchokera ku 1670 rubles.

Malo opangira Novartis Pharma amapezeka ku Basel (Switzerland), kotero kwa vildaglippin mtengo wake uzikhala molingana ndi European, koma motsutsana ndi maziko amitengo ya analogues imawoneka yokwera mtengo. Wodwala matenda ashuga apakati amatha kugula mapiritsi 28 a 50 mg kwa ma ruble 750-880.

Pulofesa S.A. Dogadin, Chief Endocrinologist wa ku Krasnoyarsk Territory, akuwona kuti ndikofunikira kuti odwala azitha kupeza matekinoloje komanso luso lotha kulandira chithandizo cha vildagliptin kwaulere. Tikudikirira kuti awonekere pamndandanda wokonda boma. Mpaka pano, mankhwalawa akuphatikizidwa pamndandanda woterezi m'magawo makumi anayi a Russian Federation ndipo malingaliro operekera odwala matenda ashuga akuchulukirachulukira.

Pulofesa Yu.Sh. Halimov, Chief Doctor-Endocrinologist wa ku St. Petersburg, akuti vildagliptin ndi yodalirika pakuyenda kwayekha, mwangwiro mu duet, sichingakhale chopambana. Incretin ndi chida chodziwikiratu mu orchestra ya antidiabetesic therapy, yomwe imatha kukhala ndi chitsulo chotsogolera ngakhale dokotala wopanda nzeru.