I-VILDAGLIPTIN - IMIYALO YOKUSEBENZISA, INTENGO, UKUBUYEKEZWA KANYE NAMA-ANALOGUES

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Isifo sikashukela sohlobo lwesibili lwesifo ngeke silawule ushukela kuphela ngosizo lokudla okune-carb ephansi kanye nokuzivocavoca okwenziwe ngomzimba. Ukusebenza kwama-pancreas kuya kubi njalo ngonyaka. Ezimweni ezinjalo, amaphilisi we-vildagliptin, umuthi wesizukulwane esisha we-hypoglycemic onomshini oyingqayizivele ongavuseleli noma ovimbela, kepha ubuyisela ubudlelwane ngaphakathi kwesikebhe phakathi kwamaseli we-α kanye ne-β amaseli we-pancreas, angasiza.

Ngabe kusebenza kangakanani futhi kuphephile ukusetshenziswa isikhathi eside, futhi iyiphi indawo lapho i-vildagliptin ihlala khona phakathi kwama-analog bendabuko namanye ama-antidiabetesic agents?

Umlando we-incretin

Ngo-1902, eLondon, oprofesa ababili bokuzivocavoca komzimba eyunivesithi u-Ernest Starling noWilliam Bylize bathola into ethile esiswini sesisu sengulube esivusa amanyikwe. Iminyaka emithathu idlulile kusuka ekutholakaleni okungabonakali kuya ekuqalisweni kwayo kwangempela. Ngo-1905, uDkt Benjamin More waseLiverpool wanquma isiguli sohlobo 2 sikashukela ngokukhishwa kolwelwesi lwe-mucous duodenum 14 g kathathu ngosuku. Ngenyanga yokuqala yokwelashwa okunjalo, ushukela kumchamo wehle ukusuka ku-200 g kuya ku-28 g, kwathi ngemuva kwezinyanga ezi-4 awuzange unqunywe nakancane ekuhlaziyeni, isiguli sibuyele emsebenzini.

Umbono awutholanga ukuthuthuka okuqhubekayo, ngoba ngaleso sikhathi bekuneziphakamiso eziningi ezahlukahlukene zokuthi kufanele baphathwe kanjani abantu abanesifo sikashukela, kepha konke kwagqitshwa ukutholwa kwe-insulin ngo-1921, okwathi isikhathi eside kwenzeka konke okwenzekayo. Ukucwaninga nge-incretin (into ebizwa ngokuthi i-mucus engxenyeni ephezulu yamathumbu we-porcine) kwaqhubeka kuphela ngemuva kweminyaka engama-30.

Eminyakeni engama-60 yekhulu leminyaka eledlule, oprofesa uM. Perley noH. Elric baveze umphumela we-incretin: ukukhiqizwa kwe-insulin okwandayo ngemuva komthwalo weglucose womlomo kuqhathaniswa nokufakwa kwe-intravenous.

Eminyakeni yama-70s, kwakhonjwa i-insulinotropic polypeptide (HIP) ye-glucose, futhi izindonga zamathumbu zihlangana. Imisebenzi yakhe ukukhulisa i-biosynthesis ne-glucose-secretion esetshenziswayo ye-insulin, kanye ne-hepatic lipogenesis, izicubu zomzimba nezicubu ze-adipose, ukwanda kwamaseli e-P, kukhulisa ukuzwela kwabo ku-apoptosis.

Eminyakeni yama-80s, kwavela ukushicilelwa kohlobo lwe-1 glucagon-peptide (GLP-1), amaseli we-L avela ku-proglucagon. Iphinde ibe nomsebenzi we-insulinotropic. USolwazi G. Bell uchaze isakhiwo saso futhi waveza i-vector entsha yokufuna indlela yasekuqaleni yokwelashwa kwesifo sikashukela (ngokuqhathaniswa namalungiselelo we-metformin wendabuko kanye nokulungiswa kwe-sulfanylurea).

Isikhathi sama -retretins sikhuphuka ngonyaka we-2000, lapho ukuphela komhlaba kungasenzeki futhi, futhi nomyalezo wokuqala wethulwa e-US Congress lapho uProfesa Rottenberg akhombisa ukuthi into ethile i-DPP 728 ngokunamandla, noma ngabe kukudla kangakanani, kuvimbela i-DPP-4 kubantu.

Umqambi we-inhibitor yokuqala ye-DPP 728 (vildagliptin) kwakungu-Edwin Willhauer, osebenza elabhorethri yesayensi yenkampani yaseSwitzerland iNovartis.

I-molecule iyathakazelisa ngoba ibopha ngokucace bha umoya-mpilo ku-amino acid obhekene nomsebenzi wokuhlaziya i-enzyme yomuntu we-DPP-4.

Umuthi uthole igama lawo ezinhlamvwini ezintathu zokuqala zesibongo sawo - i-VIL, YES - iDipeptidyl Amine Peptidase, i-GLI - isijobelelo esetshenziswa yi-WHO kwezidakamizwa ezilwa nesifo sikashukela, i-TIN - isimamva esibonisa i-enhibme inhibitor.

Lokhu kufinyelela kungabukwa nomsebenzi kaProfessor E. Bossi, lapho ethi ukusetshenziswa kwe-vildagliptin ene-metformin kwehlisa izinga le-glycosylated hemoglobin ngamaphesenti angaphezu kwe-1. Ngaphezu kokuncipha okunoshukela okunamandla, isidakamizwa sinamanye amathuba:

Yehlisa amathuba okuba ne-hypoglycemia ngezikhathi eziyi-14, uma uyiqhathanisa nokususelwa kwe-sulfonylurea (PSM);
Ngenkambo ende yokwelashwa, isiguli asitholi isisindo;
Kuthuthukisa ukusebenza kwe-β-cell.

Umuthi usukile ekunciphiseni okulula koshukela egazini kuya emiphumeleni ye-pathophysiological exhomeke ku-glucose usebenzisa bonke ubuchwepheshe besimanje.

Ngokungafani nama-algorithms aseMelika abeka i-vildagliptin emgqeni wesi-2 wezidakamizwa ezinciphisa ushukela, odokotela baseRussia babeka ama-insretin ezindaweni ezi-1-2 kuya lapho bekhetha izidakamizwa ze-hypoglycemic, yize iqiniso lokuthi ezingabizi kakhulu namuhla ngama-sulfonylureas.

IVildagriptin (igama lomkhiqizo walesi sidakamizwa nguGalvus) yavela emakethe yemithi yaseRussia ngonyaka we-2009.

Ososayensi baseRussia baphetha ngokuthi kuyadingeka ukuthi bakhethe inhlanganisela yokwenza ukuthi i-glycemia ibuye ibe ejwayelekile kanye nezinhlobo eziningana zezidakamizwa ezithinta izindlela ezahlukahlukene zokuthuthuka kwalesi sifo (i-insensitivity, i-insulin, i-glucagon synthesis). Ekuqaleni, lapho i-glycosylated hemoglobin isivele ingaphezulu kwe-9%, lapho kungekho zimpawu zomtholampilo zokuqothuka noma ngokuqina kohlobo lokwelashwa, inhlanganisela yezidakamizwa ezingama-2-4 inokwenzeka.

Izici Zemithi yeVildagliptinum

I-Vildagliptin (eresiphi, ngesiLatini, iVildagliptinum) iyinhlangano emele isigaba sezidakamizwa ze-hypoglycemic eziklanyelwe ukukhuthaza iziqhingi zeLangerhans futhi inqande i-dipeptidyl peptidase-4 ngokuzikhethela. Le enzyme inethonya elicindezelayo kuhlobo lwe-glucagon-hlobo 1 peptide (GLP-1) ne-glucose-insulinotropic polypeptide (HIP) (ngaphezu kwe-90%). Ukunciphisa umsebenzi wayo, i-incretin isheshisa ukukhiqizwa kwe-GLP-1 ne-HIP kusuka emathunjini kuya egazini phakathi nosuku. Uma okuqukethwe kwe-peptide kusondele kokujwayelekile, amaseli ama-β-cell athambekele kakhulu eglucose, futhi umkhiqizo we-insulin uyanda. Izinga lomsebenzi wama-β-cell lilingana ngqo nokuphepha kwabo. Lokhu kusho ukuthi kuma-nondiabetics, ukusetshenziswa kwe-vildagliptin ngeke kuthinte ukwakheka kwe-insulin neglucometer. Umthamo we-50-100 mg / usuku lwabanesifo sikashukela. inikeza ukwanda okuqhubekayo kokusebenza kahle kwama-β-cell.

Ngaphezu kwalokho, lapho umuthi uvuselela ukukhiqizwa kwe-GLP-1 peptide, ukwanda kwe-glucose nakho kuyanda kuma-α-cell enza umthelela we-glucagon ube namandla. I-Hyperglucagonemia idlala indima enkulu ekwakhiweni kwezinqubo ezalandela ze-pathological. Ukuhluka kwesidakamizwa ukuthi ayigcini nje ngokuvuselela izinqubo, ibuyisela ukusebenza kwamaseli we-α kanye ne-β. Lokhu akuqinisekisi ukusebenza kwayo kuphela, kepha nokuphepha nokusetshenziswa isikhathi eside.

Ngokwandisa okuqukethwe kwe-GLP-1, i-vildagliptin ithuthukisa ukuzwela kwama-α-cell ku-glucose. Lokhu kusiza ukulawula ukukhiqizwa kwe-glucagon, ukuyinciphisa ngesikhathi sokudla kunciphisa ukumelana ne-insulin.

Ukwanda kwesilinganiso se-insulin / glucagon nge-hyperglycemia ngokumelene nesizinda sokuqukethwe okuphezulu kwe-GLP-1 ne-GUI kuphakamisa ukuncishiswa kokugcinwa kwesibindi kwe-glycogen nganoma yisiphi isikhathi, noma ngabe kudla kangakanani.

Zonke lezi zinto zinikeza ukulawulwa okuzinzile kwe-glycemic.

Okunye futhi kuzothuthukiswa yi-lipid metabolism, noma kungekho ukuxhumana okuqondile phakathi komphumela kuma-peptides nama-β-cell kulolu daba.

Kwezinye izidakamizwa, ngokukhuphuka kokuqukethwe kwe-GLP yohlobo 1, ukukhipha okuqukethwe kunganciphisa, kepha ukusetshenziswa kwe-vildagliptin, akukho zimpawu ezifanayo ezirekhodiwe.

Izifundo ezibanzi nezinesikhathi eside ze-incretin zenziwe emazweni amaningi. Lapho kudliwe uGalvus, ama-5795 abantu abanesifo sikashukela abanesifo sohlobo 2 abathathe lesi sidakamizwa ngendlela yaso emsulwa noma behlangana nama-hypoglycemic agents baqopha ukwehla kokuzila ushukela kanye ne-glycosylated hemoglobin.

I-Pharmacokinetics ye-vildagliptin

I-bioavailability yesidakamizwa ingama-85%, ngemuva kokuphathwa ngomlomo igxila ngokushesha. Ngemuva kokuthatha iphilisi ngaphambi kokudla, okuqukethwe okuphezulu kwe-metabolite kubonwa ngemuva kwehora eli-1. Imizuzu engama-45 Uma uthatha umuthi ngokudla, ukumuncwa kwalesi sidakamizwa kwehliswa ngo-19%, nesikhathi sokuwufinyelela sikhushulwa ngemizuzu engama-45. I-inhibitor ibopha ngokuqinile kumaprotheni - yi-9% kuphela. Ngokufakwa kwe-intravenous, umthamo wokusatshalaliswa ngamalitha angama-71.

Umzila oyinhloko we-excretion we-metabolite yi-biotransformation, awethulwanga yi-cytochrome P450, ayakhi i-substrate, futhi ayivimbeli lezi isoenzymes. Ngakho-ke, amandla okusebenzisana kwezidakamizwa ku-incretin aphansi.

Cishe ama-85% we-vildagliptin akhishwe yizinso, ama-15% amathumbu asebenze. Kungakhathalekile ukuthi kuthathwa umthamo kangakanani, isigamu sokuphila sithatha amahora ama-3.

Ifomu lokukhishwa kweGalvus

Inkampani yaseSwitzerland i-Novartis Pharma ikhiqiza uGalvus kumathebulethi anesisindo esingu-50 mg. Kwinethiwekhi yamakhemisi, ungabona izinhlobo ezimbili zemithi ngokuya nge-vildagliptin. Kokunye, i-vildagliptin isebenza njengesithako esisebenzayo, kwelinye - i-metformin. Ukukhipha Amafomu:

I- "Pure" vildagliptin - 28 ithebhu. 50 mg ngamunye;
I-Vildagliptin + metformin - ithebhu engama-30. 50/500, 50/850, 50/1000 mg ngamunye.

Ukukhetha kwezokwelapha kanye nama-regimen yikhono le-endocrinologist. Nge-vildagliptin, imiyalo yokusebenzisa iqukethe uhla olulinganisiwe lwemithamo ejwayelekile. I-Incretin isetshenziselwa i-monotherapy noma ngesimo esiyinkimbinkimbi (nge-insulin, metformin neminye eminye imishanguzo yesifo sikashukela). Umthamo wansuku zonke ngu-50-100 mg.

Uma uGalvus enqunywe nge-sulfonylureas, umthamo owodwa ngosuku ngu-50 mg. Ngokuqokwa kwethebhulethi eli-1, kudakwa ekuseni, uma ngabe kubili, bese kuthi ekuseni nakusihlwa.

Nge-regimen vildagliptin + metformin + yokuphuma ye-sulfonylurea ehlanganisiwe, isilinganiso esivamile sansuku zonke sifinyelela ku-100 mg.

Isakhi esisebenzayo semithi yezinso sidalulwe ngendlela ye-metabolite engasebenzi; ukulungiswa kwamthamo kungenzeka nge-renal pathologies.

Beka ikhithi losizo lokuqala ngomuthi endaweni engafinyeleleki ekunakekeleni izingane. Izimo zokugcina izinga lokushisa - kufika ku-30 ° С, impilo yeshalofu - kuze kube yiminyaka emi-3. Kuyingozi ukuthatha izidakamizwa eziphelelwe yisikhathi, ngoba ukusebenza kwazo kuncishisiwe, futhi amathuba emiphumela emibi ayakhula.

Izinkomba zokusetshenziswa kwe-incretin

Umuthi, osenzo sawo sincike kumphumela we-incretin, bewufanele ukuncintisana ne-metformin kanye nokuphuma kwe-sulfanylurea. Kwenzelwe ukwelashwa kweziguli ezinesifo sikashukela sohlobo 2 kunoma yisiphi isigaba salesi sifo.

Kusetshenziswa njenge-monotherapy njengokungezwa kokudla okuphansi kwe-carbohydrate nemithwalo yemisipha ebunjiwe.

Kusebenza futhi kwirejimeni enezakhi ezimbili lapho kuhlangene ne-metformin, amalungiselelo e-sulfonylurea, i-insulin ne-thiazolidinedione, uma ukwelashwa kwangaphambi kwalawa mithi kungazange kunikeze umphumela oyifunayo.

Contraindication kanye nemiphumela engafuneki

IVildagliptin ibekezelelwa kalula ngabanesifo sikashukela kunamanye ama-hypoglycemic agents. Phakathi kokuphambana:

Ukungabekezelelani komuntu ngamunye kwe-galactose;
Ukuntuleka kwe-Lactose;
I-Hypersensitivity kwizithako ezisebenzayo zefomula;
IGlucose-galactose malabsorption.

Akukho datha ethembekile mayelana nomphumela we-incretin kuma-diabetesics wezingane, ngakho-ke, i-metabolite ayinqunyelwe izigaba ezinjalo zeziguli.

Lapho usebenzisa i-Galvus kunoma iyiphi indlela yokwelashwa, imiphumela emibi yaqoshwa:

Nge-monotherapy - i-hypoglycemia, ukulahleka kokuxhumana, ikhanda, ukuvuvukala, ushintsho lwesigqi sokusikeka;
I-Vildagliptin eneMetformin - ukuthuthumela kwesandla nezimpawu ezifanayo kweziyedlule;
I-Vildagliptin ene-sulfonylurea derivatives - i-asthenia (ukuphazamiseka kwengqondo) yengezwe ohlwini lwangaphambilini;
I-Vildagliptin ene-thiazolidinedione derivatives - ngaphezu kwezimpawu ezijwayelekile, ukwanda kwesisindo somzimba kungenzeka;
I-Vildagliptin ne-insulin (kwesinye isikhathi ene-metformin) - ukuphazamiseka kwe-dyspeptic, hypoglycemia, ikhanda.

Kwezinye iziguli, izikhalazo ze-urticaria, ukukhonkotha kwesikhumba kanye nokuvela kwamacembe, kubhalwe phansi ngokwengeziwe nge-pancreatitis. Ngaphandle kohlu oluqinile lwemiphumela engathandeki, amathuba okuvela kwawo mancane. Imvamisa, lokhu kwephulwa kwesimo sesikhashana kanye nokuyekiswa komuthi akudingi.

Izici zokwelashwa nge-vildagrippin

Eminyakeni engu-15 edlule, kwenziwa izifundo zokwelapha ezingama-135 zama-incretin emazweni ahlukene. Ngusiphi isigaba sokwelapha i-hypoglycemic yesifo sikashukela sohlobo 2 esibekiwe?

Ekuqaleni, lapho kudliwa ngendlela "emsulwa";
Ekuqaleni okuhlangene ne-metformin;
Lapho yengezwa ku-metformin ukuthuthukisa amandla ayo;
Enguqulweni kathathu: vildagliptin + metformin + PSM;
Lapho ihlanganiswa ne-insal insulin.

Kuzo zonke lezi zimo, ungasebenzisa i-vildagliptin. Umthamo we-200 mg / ngosuku uthathwa ngaphandle kwezinkinga. Kwezinye izimo, i-overdose kungenzeka.

Uma uthatha umthamo owodwa we-400 mg, i-myalgia, ukuvuvukala, umkhuhlane, ukubekeka kweziqubu kuyavela, izinga le-lipase liyakhuphuka.
Ngomthamo we-600 mg, imilenze iyavuvukala, okuqukethwe ngamaprotheni e-C-reactive, ALT, CPK, myoglobin ayanda. Ukuhlolwa kwesibindi kuyadingeka, uma umsebenzi we-ALT noma we-AST weqe okwejwayelekile izikhathi ezi-3, umuthi kumele uthathelwe indawo.
Uma i-hepatic pathologies (ngokwesibonelo, i-jaundice) ikhonjwa, umuthi umiswa kuze kuqedwe wonke ama-pathologies wesibindi.
Uma kwenzeka isifo sikashukela esincike ku-insulin 2, i-vildagliptin kungenzeka kuphela ngokuhambisana ne-hormone.
Musa ukusebenzisa umuthi isifo sikashukela sohlobo 1, kanye nesimo se-ketoacidosis.

Ucwaningo ngomphumela we-incretin on okuhlushwa alwenziwe.

Uma ukuphuza umuthi kuhambisana nokuphulwa kokuxhumana, kuyodingeka wenqabe ukushayela nezindlela eziyinkimbinkimbi.

Ama-analog kaGalvus nokutholakala kwawo

Phakathi kwama-analogues, i-vildagrippin inemithi enenye into esebenzayo esisekelweni kanye nendlela yokusebenza efanayo.

I-Onglisa isithako esisebenzayo ku-saxagliptin. Intengo - kusuka kuma-ruble ayi-1900;
I-Trazhenta - isithako esisebenzayo sesigliptin. Izindleko ezijwayelekile ngama-ruble ayi-1750;
I-Januvia yinto esetshenziswayo ye-sitagliptin. Intengo - kusuka kuma-ruble ayi-1670.

Izikhungo zokukhiqiza zeNovartis Pharma zitholakala eBasel (eSwitzerland), ngakho-ke i-vildaglippin intengo izohambisana nekhwalithi yaseYurophu, kepha uma isemuva kwendleko yezindleko ibukeka ingabizi. Isifo sikashukela esinemali ephakathi nendawo singathenga amaphilisi angama-28 ama-50 mg ngama-ruble ayi-750-880.

Ngokuqondene nombono wochwepheshe, odokotela abavumelani: isizukulwane esisha somuthi siphephile, kufanelekile ukusisebenzisa futhi siyasebenza.

USolwazi S.A. UFogadin, oyi-Chief Endocrinologist ye-Krasnoyarsk Territory, ubona kubalulekile ukuthi iziguli zifinyeleleke kakhulu kubuchwepheshe obusha kanye nekhono lokwelashwa nge-vildagliptin mahhala. Silinde yena ukuthi avele ohlwini olukhethayo oluhlanganisiwe. Kuze kube manje, lesi sidakamizwa sifakwa ohlwini olunjalo ezifundeni ezingamashumi amane zeRussian Federation futhi i-geography yokuhlinzeka abanesifo sikashukela ngemibandela yokukhetha iyanda.

USolwazi Yu.Sh. UHalimov, oyi-Chief Doctor-Endocrinologist yase-St. I-Incretin iyithuluzi elisezingeni lomhlaba e-orchestra yokwelapha nge-antidiabetes, elikwazi ukusebenza ngaphansi kwengqamuzana lenduku yomqhubi ngisho nodokotela ongenalwazi.

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