I-SITAGLIPTIN - IMIYALO ESETSHENZISWAYO, INTENGO, UKUBUYEKEZWA KANYE NAMA-ANALOGUES

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Kwi-pathogenesis yohlobo 2 sikashukela, izindlela ezintathu eziyinhloko ziyahlukaniswa:

Ukuqina kwe-insulin tissue;
Ukuphazamiseka ekukhiqizweni kwe-insulin endulin;
Ukuqhuma ngokweqile kweshukela kusibindi.

Isibopho sokuqalwa kwesifo esinjengalesi sinokulala ngamaseli e-b kanye nama-c of pancreas. Lokhu kubuye kukhiqize i-hormone ekhuthaza ukuguqulwa kwe-glucose ibe amandla yimisipha nobuchopho. Uma izinga lokukhiqizwa kwalo lincipha, lokhu kuthuthukisa i-hyperglycemia.

Ama-B-cell abhekene nokukhiqizwa kwe-glucagon, ukweqisa kwayo kudala izimfanelo zokufihla kwe-glucose ngokweqile kwesibindi. I-glucagon ethe xaxa kanye nokuntuleka kwe-insulin kunikeza izimo zokuqongelwa kwe-glucose engatholakali emgodini wegazi.

Ukuphathwa okusebenzayo kwesifo sikashukela sohlobo 2 akunakwenzeka ngaphandle kokuzinza nokuhlala isikhathi eside (sonke isikhathi sesifo) ukulawulwa kwe-carbohydrate metabolism. Izilingo eziningi zamazwe omhlaba ziyaqinisekisa ukuthi isinxephezelo sikashukela kuphela esinikeza izimo zokuvimbela izinkinga futhi sikhulise isikhathi sokuphila kososhukela.

Ngaphandle kwayo yonke inhlobo yezidakamizwa zokulwa nesifo sikashukela, akuzona zonke iziguli ezikwazi ukuthola isinxephezelo esimeme sama-carbohydrate ngosizo lwazo. Ngokusho kocwaningo lwe-UKPDS olugunyaziwe, ama-45% abantu abanesifo sikashukela bathole isinxephezelo esingu-100% ukuvimbela i-microangiopathy ngemuva kweminyaka emi-3, kuthi abangama-30% kuphela emva kweminyaka eyi-6.

Lobunzima bulawula isidingo sokuthuthukisa isigaba esisha sezidakamizwa esingesizukusiza kuphela ukuqeda izinkinga ze-metabolic, kepha futhi sigcine ama-pancreas, sivuselela indlela yokusebenza komzimba ukulawula ukukhiqizwa kwe-insulin kanye ne-glycemia.

Imithi yohlobo lwe-incretin engalawula isifo sikashukela sohlobo 2 ngaphandle kokukhuthaza i-pancreas, ushintsho olungazelelwe ku-glycemia, ingozi ye-hypoglycemia iyintuthuko yakamuva eyenziwe osokhemisi.

I-inhibitor ye-enzyme GLP-4 Sitagliptin isiza umuntu onesifo sikashukela ukulawula isifiso sokudla nesisindo somzimba, enikeza umzimba amandla okunqoba ngokuzimela enkingeni ye-glucose ubuthi.

Khipha ifomu nokwakheka

Umuthi osuselwe kwi-sitagliptin enegama lokuhweba u-Januvia ukhiqizwa ngendlela yamaphilisi ayindilinga ane-pink noma i-beige hue futhi umakwe u- “227” nge-100 mg, “112” nge-50 mg, “221” nge-25 mg. Izibhebhe zigcwele emabhokisini epulasitiki noma emapensela. Kungaba khona amapuleti amaningana ebhokisini.

Umuthi oyisisekelo osebenzayo wesigliptin phosphate hydrate ufakelwa i-croscarmellose sodium, i-magnesium stearate, cellulose, sodium stearyl fumarate, i-phosphate ye-calcium hydrogen engachazwanga.

Kwi-sildagliptin, intengo incike ekufakweni, ikakhulukazi kumathebulethi angama-28 udinga ukukhokha ama-ruble ayi-1,596-1724. Kunikezwa umuthi obhalwe phansi, impilo yeshalofu unyaka ongu-1. Umuthi awudingi izimo ezikhethekile zokugcinwa. Ukufakwa okuvulekile kugcinwa emnyango wesiqandisi inyanga yonke.

I-Pharmacology Sitagliptinum

I-Sitagliptin yehlukile kwezinye izidakamizwa ze-antidiabetic ekwakhiweni kwayo kokusebenza nesakhiwo sayo. Ukuvimbela amandla we-enzyme ye-DPP-4, i-inhibitor inyusa okuqukethwe kwama-incretins HIP ne-GLP-1, alawula i-glucose homeostasis.

La mahomoni akhiqizwa yi-mucosa yamathumbu, futhi ukwenziwa kwama-incretin kuyanda ngokudla izakhi zomzimba. Uma amazinga eglucose ejwayelekile futhi ephakeme, ama-hormone akhuphuka aze afike ku-80% wokukhiqizwa kwe-insulin nokugcinwa kwawo ngamaseli β-amaseli ngenxa yezindlela zokusayina emangqamuzaneni. I-GLP-1 inqanda ukuvikela okuphezulu kwe-glucagon hormone ngama-b-cell.

Ukwehla kokuxineka kwe-glucagon ngokumelene nesizinda sokwenyuka kwesibalo se-insulin kuqinisekisa ukuncishiswa kokushukela kwe-glucose esibindini. Lezi zinqubo futhi uqinisekise ukuguquguquka kwe-glycemia. Umsebenzi wama-incretins ukhawulelwe ngemuva kwesizinda esithile somzimba, ikakhulukazi nge-hypoglycemia, azithinti ukwakheka kwe-glucagon ne-insulin.

Kusetshenziswa i-DPP-4, ama-incretin angama-hydrolyzed ukwenza i-inert metabolites. Ukucindezela umsebenzi walesi enzyme, i-sitagliptin inyusa okuqukethwe kwama-incretin ne-insulin, kunciphisa ukukhiqizwa kwe-glucagon.

Nge-hyperglycemia, enye yezimpawu eziphambili zesifo sikashukela sohlobo 2, le ndlela yokusebenza isiza ukwehlisa izinga le-hemoglobin ye-glycated, ushukela olambile noshukela ngemuva komthwalo we-carbohydrate. Umthamo owodwa we-sitagliptin uyakwazi ukuvimba ukusebenza kwe-DPP-4 ngosuku, okwandisa ukujikeleza kwama-incretin egazini izikhathi ezi-2-3.

I-Pharmacokinetics ye-sitagliptin

Ukufakwa kwesidakamizwa kwenzeka ngokushesha, nge-bioavailability ka-87%. Izinga lokumunca alixhomeki esikhathini sokudla kanye nokwakheka kokudla, ikakhulukazi, ukudla okunamafutha akushintshi imingcele ye-pharmacokinetic ye-incretin mimetic.

I-inhibitor ifinyelela izinga layo eliphakeme (950 nmol) emahoreni ayi-11.5 I-AUC incike kumthamo, ukungafani phakathi kwezigaba ezahlukahlukene zabanesifo sikashukela kuphansi.

Ngokulingana, ukusetshenziswa okungeziwe kwethebhulethi eyi-100 mg kukhulisa indawo ngaphansi kwejika le-AUC, elibonakalisa ukuthembela kokusatshalaliswa kwenani ngesikhathi, ngo-14%. Umthamo owodwa wamathebhulethi ayi-100 mg uqinisekisa umthamo wokusabalalisa we-198 l.

Ingxenye encane kakhulu ye-incretin mimetic iyakhiwa. Kutholwe ama-metabolites ayi-6 aswele amandla okuvimbela i-DPP-4. Ukuqashwa kabusha kweRenal (QC) - 350 ml / amaminithi. Ingxenye eyinhloko yesidakamizwa isuswa izinso (i-79% ifomu elingaguquki kanye ne-13% ngendlela yama-metabolites), okusele kudonswa ngamathumbu.

Uma ubheka umthwalo osindayo ezinso ezinsweni zikashukela ezinesifo esingamahlalakhona (CC - 50-80 ml / min.), Izinkomba ziyefana, ngeCC 30-50 ml / min. ukuphindwa kwamanani we-AUC kwabonwa, kune-CC ngaphansi kwama-30 ml / min. - amahlandla amane. Izimo ezinjengalezi ziphakamisa ukuguqulwa kwesilinganiso.

Nge-hepatic pathologies yokuqina okulinganiselayo, i-Cmax ne-AUC inyuka ngo-13% no-21%. Ngezimo ezibucayi, i-pharmacokinetics ye-sitagliptin ayiguquki kakhulu, ngoba umuthi ngokuyinhloko udlulwa izinso.

Ku-diabetesics yobudala obuvuthiwe (iminyaka engama-65-80), amapharamitha we-pharmacokinetic wokunyuka kwe-incretin mimetic ngo-19%. Amanani anjalo awabalulekanga ngokomtholampilo, ngakho-ke ukunikwa imali okwejwayelekile akudingekile.

Ngubani okhonjiswa i-incretinomimetic

Umuthi unqunyelwe isifo sikashukela sohlobo 2 ngaphezu kokudla okune-carb ephansi kanye nomsebenzi owanele wemisipha.

Isetshenziswa njengesidakamizwa esisodwa nokwelashwa okuhlangene ne-metformin, amalungiselelo e-sulfonylurea noma i-thiazolidinediones. Kungenzeka futhi ukusebenzisa amarejista wokujova kwe-insulin uma le ndlela isiza ukuxazulula inkinga yokumelana ne-insulin.

Contraindication ye-sitagliptin

Musa ukunquma umuthi:

Ngokuzwela okukhulu komuntu ngamunye;
Isifo sikashukela esinesifo sohlobo 1;
Ukhulelwe futhi uncelisa ibele;
Esimweni se-ketoacidosis yesifo sikashukela;
Ezinganeni.

Abantu abanesifo sikashukela abanesimo esingamahlalakhona se-renal pathology badinga ukunakwa okukhethekile.

Ungayithatha kanjani

Nge-sitagliptin, imiyalo yokusebenzisa itusa ukuphuza umuthi ngaphambi kokudla. Imithamo ejwayelekile iyafana kunoma yiluphi uhlobo lokwelashwa - 100 mg / ngosuku. Uma uhlelo lokwamukelwa luphukile, iphilisi kufanele lidakwe nganoma yisiphi isikhathi, ukuphinda kabili le doti akwamukeleki.

NgeCC 30-50 ml / imizuzu. umthamo wokuqala womuthi uzoba ngaphansi amahlandla ama-2 - ama-50 mg / usuku., ne-CC ngaphansi kwe-30 ml / min. - Izikhathi ezi-4 - 25 mg / ngosuku. (isikhathi esisodwa). Isikhathi se-hemodialysis asithinti irejimendi yokwelapha i-sitagliptin.

Imicimbi Emibi

Uma kuqhathaniswa nokubuyekezwa, iningi labo bonke abanesifo sikashukela bakhathazekile nge-dyspepsia, isitulo esidangelekile. Ekuhlolweni kwelebhu, i-hyperuricemia, ukwehla kokusebenza kahle kwe-yegilo gland, kanye ne-leukocytosis kuyaphawulwa.

Phakathi kweminye imiphumela engalindelekile (ubudlelwane ne-incretin mimetic abukafakazelwa) - izifo zokuphefumula, i-arthralgia, i-migraine, i-nasopharyngitis). Isigameko se-hypoglycemia siyefana nemiphumela eqenjini lokulawulwa kwe-placebo.

Siza ngokweqile

Uma kwenzeka kweqa ngokweqile, umuthi ongaphekiwe ususwa emgudwini wesisu, wonke amapharamitha abalulekile (kufaka ne-ECG) ayaqashwa. Izimpawu ezibonakalayo nezisekelayo zikhonjisiwe, kufaka phakathi i-hemodialysis enamakhono okuhlala isikhathi eside (imithamo engu-13.5 yesidakamizwa isuswa emahoreni angama-3-4).

Imiphumela Yokusebenzelana Kwezidakamizwa

Ngokusebenzisa kanyekanye i-sitagliptin nge-metformin, i-rosiglitazone, izindlela zokuvimbela inzalo ngomlomo, i-glibenclamide, i-warfarin, i-simvastatin, ama-pharmacokinetics aleli qembu lezidakamizwa awashintshi.

Ukuphathwa kanyekanye kwe-sitagliptin nge-digoxin akusho ukuthi ushintsho kumthamo wemithi. Kunconyelwa okufanayo ngokufundiswa nokuxhumana kwe-sitagliptin ne-cyclosporin, ketoconazole.

I-Sildagliptin - i-analogues

ISitagliptin igama lomhlaba wonke lesi sidakamizwa; igama laso lokuhweba yiJanuvius. I-analogue ingabhekwa njengemithi ehlanganisiwe yeYanumet, efaka i-sitagliptin ne-metformin. UGalvus ungoweqembu lama-DPP-4 inhibitors (i-Novartis Pharma AG, Switzerland) enesakhi esisebenzayo i-vildagliptin, amanani ama-ruble angama-800.

Izidakamizwa ze-Hypoglycemic nazo zilungele ikhodi ye-ATX yezinga 4:

INesina (Takeda Pharmaceuticals, e-USA, ngokusekelwe ku-alogliptin);
I-Onglisa (Inkampani yeBristol-Myers squibb, isuselwa ku-saxagliptin, intengo - ama-ruble ayi-1800);
I-Trazhenta (iBristol-Myers squibb Inkampani, e-Italy, eBrithani, ene-nthogliptin esebenzayo yezinto), intengo - ama-ruble ayi-1700.

Le mishanguzo ebaluleke kakhulu ayifakwanga ohlwini lwemithi ekhethwayo; kufanelekile yini ukuzihlola ngobungozi bakho nengozi yesabelomali sakho nezempilo?

I-Sitagliptin - izibuyekezo

Uma kuqhathaniswa nemibiko ezinhlanganweni ezithinta iziqu, uJanuvius uvame ukunqatshelwa kwabanesifo sikashukela esigabeni sokuqala salesi sifo. Mayelana ne-sitagliptin, ukubuyekezwa kodokotela neziguli kukhombisa ukuthi ukusetshenziswa kwe-incretinomimetic kunama-nuances amaningi.

UJanuvia umuthi wesizukulwane esisha futhi akubona bonke odokotela abaye bathola ulwazi olwanele lokuyisebenzisa. Kuze kube muva nje, i-metformin ibiyisidakamizwa sohlanga lokuqala; manje uJanuvia ubizwa ngokuthi yi-monotherapy. Uma amandla ayo enele, ukungezelela nge-metformin nezinye izidakamizwa akuseluleki.

Isifo sikashukela sikhononda ukuthi umuthi awuhlali uhlangabezana nezidingo ezishiwo, ngokuhamba kwesikhathi ukusebenza kwawo kuncipha. Inkinga lapha akukhona ukujwayela amaphilisi, kepha izici zesifo: uhlobo lwesifo sikashukela esiyi-pathology esingapheliyo futhi esithuthukayo.

I-Eugene, i-Lipetsk. Ekugcineni udokotela wami uphumile eholidini. Ngabheka idayari yami yokulawula ushukela, eqondiselwe ama-kebabs. Ukuhlaziywa kwakungekubi, futhi wasikisela ukuthi ngithathe iDiabeteson MV ngeJanuvia. I-endocrinologist yami inolwazi, iyayiqaphela yonke imikhiqizo emisha. Yini inzuzo yayo, ngaphandle kwezindleko (izikhathi ezi-6 ngaphezulu!), Angisaqondi. Ngiphuza iphilisi likaJanuvia ekuseni inyanga, amanye ayi-3 ayiSiofora 500. Ushukela olambile manje awusekho ngaphezulu kuka-7 mmol / l, futhi usheshe ubuye usujwayele ngemuva kokudla. Phambilini, ngemuva kokuqeqeshwa kakhulu ejimini, ushukela wehla kakhulu. Manje ifinyelela okujwayelekile (5.5 mmol / l) bese ikhuphuka kancane. Ngokwesilinganiso, benginezinkomba ezifanayo ngaphambili, kepha ama-ushukela anciphile impela. Akukho engingakusho ngemiphumela emibi - ngisebenzise inyanga ezolile.

Yonke imibono iholela esiphethweni sokuthi ukwethulwa kwe-sitagliptin ekusebenzeni ngokomtholampilo, okubonisa isigaba esisha sezidakamizwa, kunikeza ithuba elanele lokuphatha isifo sikashukela sohlobo 2 kunoma yisiphi isigaba, kusukela prediabetes kuya ekwelashweni okungeziwe, ngemiphumela engagculisi ngokusetshenziswa kwezikimu zesinxephezelo se-glycemic sendlela.

Umbiko ngoProfesa A.S. I-Ametov, i-endocrinologist-diabetesologist mayelana nemfundiso kanye nokuzilolonga ngokusebenzisa i-sitagliptin - kuvidiyo.

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