Malangizo ogwiritsira ntchito "Pioglitazone", magwiridwe antchito, mapangidwe, analogi, mitengo, zofunikira, zotsutsana, zoyipa ndi kuwunika

Buku lamalangizo

• Wogwirizira Matifiketi Olembetsa: Ranbaxy Laboratories, Ltd. (India)

Wothandizira pakamwa wa hypoglycemic, wachokera pagulu la thiazolidinedione. Agonist wamphamvu, wosankha wamphamvu wa gamma receptors yokhazikitsidwa ndi peroxisome proliferator (PPAR-gamma). PPAR gamma receptors imapezeka mu adipose, minofu minofu ndi chiwindi. Kutsegula kwa ma nyukiliya okwanira PPAR-gamma modulates kusindikizidwa kwa majini angapo amtundu wa insulin omwe amathandizira kuwongolera kwa glucose ndi lipid metabolism. Imachepetsa kukana kwa insulini mu zotumphukira ndipo mu chiwindi, chifukwa cha izi pali kuwonjezeka kwa kumwa kwa glucose wodalira insulin komanso kuchepa kwa kupanga kwa glucose m'chiwindi. Mosiyana ndi zotumphukira za sulfonylurea, pioglitazone simalimbikitsa kubisalira kwa insulin mwa maselo a pancreatic beta.

Mtundu wachiwiri wa matenda a shuga a mellitus (osadalira insulini), kuchepa kwa kukana insulini pansi pa zochita za pioglitazone kumapangitsa kuchepa kwa ndende ya magazi, kuchepa kwa plasma insulin ndi hemoglobin A 1c (glycated hemoglobin, HbA 1c).

Mtundu wachiwiri wa matenda a shuga a mellitus (osadalira insulini) omwe ali ndi vuto la lipid metabolism lomwe limagwirizanitsidwa ndi kugwiritsa ntchito pioglitazone, pali kuchepa kwa TG komanso kuwonjezeka kwa HDL. Nthawi yomweyo, mulingo wa LDL ndi cholesterol yathunthu mwa odwala sasintha.

Pambuyo pakulowetsa pamimba yopanda kanthu, pioglitazone amadziwika m'madzi am'madzi pambuyo pa mphindi 30. C max mu plasma imafikiridwa pambuyo pa maola 2. Mukamadya, panali kuwonjezeka pang'ono kwa nthawi kuti afike C max mpaka maola 3-4, koma kuchuluka kwa mayeso sikunasinthe.

Pakadutsa kamodzi, mawonekedwe a V d a pioglitazone pafupifupi 0,63 ± 0,41 l / kg. Kumangiriza mapuloteni a seramu a anthu, makamaka okhala ndi albumin, ndi oposa 99%, kumangiriza mapuloteni ena a seramu sikumatchulidwa kokwanira. Ma metabolites a pioglitazone M-III ndi M-IV amakhudzidwanso kwambiri ndi serum albin - oposa 98%.

Pioglitazone imapangidwa kwambiri mu chiwindi ndi hydroxylation ndi oxidation. Metabolites M-II, M-IV (hydroxy derivatives of pioglitazone) ndi M-III (keto ofanana ndi pioglitazone) amawonetsa zochitika zam'magulu azikhalidwe zamtundu wa shuga. Ma metabolabolites nawonso amasinthidwa pang'ono kukhala ma conjugates a glucuronic kapena sulfuric acid.

Kagayidwe ka pioglitazone mu chiwindi kumachitika ndi nawo gawo la isoenzymes CYP2C8 ndi CYP3A4.

T 1/2 ya pioglitazone yosasinthika ndi maola 3-7, pioglitazone yathunthu (pioglitazone ndi metabolites yogwira) ndi maola 16-24. Chilolezo cha pioglitazone ndi 5-7 l / h.

Pambuyo pakukonzekera pakamwa, pafupifupi 15-30% ya mlingo wa pioglitazone umapezeka mkodzo. Pioglitazone ochepa kwambiri amachotsedwa ndi impso, makamaka mu mawonekedwe a metabolites ndi ma conjugates. Amakhulupirira kuti akamwetsa, muyezo umodzi umapukusidwa mu ndulu, zonse osasinthika komanso mawonekedwe a metabolites, ndikuchotsa m'thupi ndi ndowe.

The wozungulira pioglitazone ndi yogwira metabolites mu seramu magazi kukhalabe wokwanira okwanira maola 24 pambuyo limodzi makonzedwe a tsiku ndi tsiku mlingo.

Lembani matenda ashuga a 2 a mellitus (osadalira insulini).

Tengani pakamwa 30 mg 1 nthawi / tsiku. Kutalika kwa chithandizo kumayikidwa payekhapayekha.

Mulingo woyenera wophatikiza mankhwala ndi 30 mg / tsiku.

Kuchokera kumbali ya kagayidwe: hypoglycemia ikhoza kupangika (kuyambira pang'ono mpaka pakali).

Kuchokera ku hemopoietic dongosolo: kuchepa magazi, kuchepa kwa hemoglobin ndi hematocrit ndikotheka.

Kuchokera pamimba yogaya: kawirikawiri - kuchuluka kwa ALT ntchito.

Pioglitazone imaphatikizidwa pakatundu ndi pakati.

Odwala omwe ali ndi insulin, ndipo amayambira kuzungulira pang'onopang'ono, mankhwalawa ndi thiazolidatediones, kuphatikizapo pioglitazone, amatha kuyambitsa mazira. Izi zimawonjezera chiopsezo cha kutenga pakati ngati kulera koyenera sikugwiritsidwa ntchito.

Mu kafukufuku woyeserera nyama, zidawonetsedwa kuti pioglitazone ilibe mphamvu ndipo siziwononga chonde.

Mukamagwiritsa ntchito mtundu wina wa thiazolidinedione munthawi yomweyo ndi njira zakulera zamkamwa, kuchepa kwa kuchuluka kwa ethinyl estradiol ndi norethindrone mu plasma kumawonedwa ndi pafupifupi 30%. Chifukwa chake, pogwiritsa ntchito munthawi yomweyo kugwiritsa ntchito pioglitazone ndi njira zakulera zamkamwa, ndizotheka kuchepetsa mphamvu zakulera.

Ketoconazole linalake ndipo limalepheretsa chiwindi kuphatikizika kwa pioglitazone.

Pioglitazone sayenera kugwiritsidwa ntchito pamaso pazowoneka bwino za matenda a chiwindi mu gawo logwira kapena kuwonjezeka kwa ntchito ya ALT 2,5 kuposa VGN. Ndi ntchito yokwezeka kwambiri ya michere ya chiwindi (ALT yotsika kuposa 2G kuposa VGN), odwala amayenera kuwunika asanachitike kapena nthawi ya chithandizo ndi pioglitazone kuti adziwe chomwe chikuwonjezera. Ndi kuwonjezeka kwapang'onopang'ono kwa ntchito ya enzyme ya chiwindi, chithandizo chiyenera kuyambitsidwa mosamala kapena kupitiriza. Pankhaniyi, kuwunikira pafupipafupi chithunzi cha kuchipatala ndikuwonetsetsa momwe ntchito ya chiwindi imayendera.

Pankhani yowonjezereka yogwira ntchito ya transaminases mu seramu (ALT> 2.5 nthawi yayitali kuposa VGN), kuwunikira ntchito ya chiwindi kuyenera kuchitika pafupipafupi mpaka msana ubwerere kwazomwe zikuyambira kapena ku zisonyezo zomwe zimawonedwa kale chithandizo. Ngati ntchito za ALT ndizokwera katatu kuposa VGN, ndiye kuti kuyesa kwachiwiri kuti mupeze ntchito ya ALT kuyenera kuchitika posachedwa. Ngati zochitika za ALT zikadatsala pang'ono 3 times> VGN pioglitazone ziyenera kusiyidwa.

Pa mankhwala, ngati mukukayikira kuti chitukuko cha chiwindi chimayambitsa matenda (mawonekedwe a nseru, kusanza, kupweteka kwam'mimba, kutopa, kusowa kwa chakudya, mkodzo wakuda), kuyesa kwa chiwindi kuyenera kutsimikizika. Lingaliro la kupitiriza kwa pioglitazone mankhwala liyenera kutengedwa pamaziko a zidziwitso zamankhwala, poganizira magawo a labotale. Pankhani ya jaundice, pioglitazone iyenera kusiyidwa.

Pioglitazone sayenera kugwiritsidwa ntchito pamaso pazowoneka bwino za matenda a chiwindi mu gawo logwira kapena kuwonjezeka kwa ntchito ya ALT 2,5 kuposa VGN. Ndi ntchito yokwezeka kwambiri ya michere ya chiwindi (ALT yotsika kuposa 2G kuposa VGN), odwala amayenera kuwunika asanachitike kapena nthawi ya chithandizo ndi pioglitazone kuti adziwe chomwe chikuwonjezera. Ndi kuwonjezeka kwapang'onopang'ono kwa ntchito ya enzyme ya chiwindi, chithandizo chiyenera kuyambitsidwa mosamala kapena kupitiriza. Pankhaniyi, kuwunikira pafupipafupi chithunzi cha kuchipatala ndikuwonetsetsa momwe ntchito ya chiwindi imayendera.

Pankhani yowonjezereka yogwira ntchito ya transaminases mu seramu (ALT> 2.5 nthawi yayitali kuposa VGN), kuwunikira ntchito ya chiwindi kuyenera kuchitika pafupipafupi mpaka msana ubwerere kwazomwe zikuyambira kapena ku zisonyezo zomwe zimawonedwa kale chithandizo. Ngati ntchito za ALT ndizokwera katatu kuposa VGN, ndiye kuti kuyesa kwachiwiri kuti mupeze ntchito ya ALT kuyenera kuchitika posachedwa. Ngati zochitika za ALT zikadatsala pang'ono 3 times> VGN pioglitazone ziyenera kusiyidwa.

Pa mankhwala, ngati mukukayikira kuti chitukuko cha chiwindi chimayambitsa matenda (mawonekedwe a nseru, kusanza, kupweteka kwam'mimba, kutopa, kusowa kwa chakudya, mkodzo wakuda), kuyesa kwa chiwindi kuyenera kutsimikizika. Lingaliro la kupitiriza kwa pioglitazone mankhwala liyenera kutengedwa pamaziko a zidziwitso zamankhwala, poganizira magawo a labotale. Pankhani ya jaundice, pioglitazone iyenera kusiyidwa.

Mosamala, pioglitazone iyenera kugwiritsidwa ntchito kwa odwala omwe ali ndi edema.

Kukula kwa kuchepa kwa magazi m'thupi, kuchepa kwa hemoglobin ndi kuchepa kwa hematocrit kungalumikizidwe ndi kuchuluka kwa plasma ndipo sikuwonetsa zovuta zamatenda ena.

Ngati ndi kotheka, kugwiritsa ntchito nthawi imodzi ya ketoconazole iyenera kuwunika kuchuluka kwa glycemia.

Zowopsa zochepa za kuchuluka kwakanthawi kwamachitidwe a CPK adadziwika motsutsana ndi kugwiritsa ntchito pioglitazone, komwe kunalibe zotsatirapo za chipatala. Ubwenzi wamachitidwe awa ndi pioglitazone sichikudziwika.

Miyezo yapakati ya bilirubin, AST, ALT, alkaline phosphatase ndi GGT inachepa pakuwunika kumapeto kwa chithandizo cha pioglitazone poyerekeza ndi zofananira zofananira asanalandire chithandizo.

Musanayambe chithandizo komanso chaka choyamba chamankhwala (miyezi iwiri iliyonse) komanso nthawi ndi nthawi, zochitika za ALT ziyenera kuyang'aniridwa.

M'maphunziro oyesera, pioglitazone si mutagenic.

Kugwiritsa ntchito pioglitazone mwa ana sikulimbikitsidwa.

Kutulutsa Fomu

"Pioglitazone" imapezeka mu mapiritsi a 15, 30 ndi 45 mg. Chidacho chikuvomerezedwa ku Russia kuti chithandizire matenda a shuga 2, kaya akhale monotherapy, kapena kuphatikiza ena othandizira pakamwa kapena a insulin. Ku EU, pali mitundu yambiri yamankhwala: mankhwalawa amayenera kugwiritsidwa ntchito pokhapokha ngati palibe chithandizo.

Pharmacodynamics ndi pharmacokinetics: malongosoledwe amchitidwewo

Mu 1999, mankhwala adavomerezeka kuti agulitse. Mu 2010, rosiglitazone adachotsedwa pamsika potsatira lingaliro la European Medicines Agency atazindikira kuti zimayambitsa chiwopsezo cha mtima. Kuyambira 2010, pioglitazone ndiye chokha chogulitsidwa, ngakhale chitetezo chake chikukayikira ndikugwiritsa ntchito koletsedwa m'maiko angapo, kuphatikiza France, chifukwa chakutha kwa khansa.

Thiazolidinediones - gulu la mankhwala omwe amachititsa maselo amthupi kugwira ntchito ya insulin. Sizikhudza kubisika kwa insulini mu kapamba. Mankhwalawa amamangirira ku receptor ya nyukiliya m'chiwindi, mafuta ndi minofu yam'mimba, zomwe zimapangitsa kuti insulor receptors iwonjezeke, motero, kumva. M'matizi awa, mayamwidwe ndi kuwonongeka kwa glucose zimathandizira, ndipo gluconeogeneis amachepetsa.

Pambuyo pakukonzekera pakamwa, kuchuluka kwa plasma kumatheka patatha maola awiri. Zakudya zimachedwa mayamwidwe, koma osachepetsa kuchuluka kwa zosakaniza zomwe zimagwira. Bioavailability ndi 83%. Mankhwalawa ndi hydroxylated ndi oxid m'chiwindi kudzera mu dongosolo la cytochrome P450. Mankhwalawa amakonzedwa makamaka ndi CYP2C8 / 9 ndi CYP3A4, komanso CYP1A1 / 2. Atatu mwa asanu ndi amodzi a metabolites omwe ali odziwika bwino amagwira ntchito ndipo ali ndi vuto la hypoglycemic. Hafu ya moyo wa chinthucho chimachokera ku maola 5 mpaka 6, ndipo metabolite yogwira imayambira maola 16 mpaka 24. Ndi kuperewera kwa hepatic, ma pharmacokinetics amasintha mosiyanasiyana, mu plasma yaulere, yopanda protein ya pioglitazone imawonjezeka.

Zizindikiro ndi contraindication

Pafupifupi anthu 4,500 omwe ali ndi matenda a shuga a 2 adatenga pioglitazone ngati gawo lawofufuza. Mwanjira ya monotherapy, pioglitazone nthawi zambiri anali kuyerekeza ndi placebo. Kuphatikiza kwa pioglitazone ndi sulfonylureas, metformin ndi insulin kwayesedwanso bwino. Kusanthula kwa Meta kumaphatikizapo maphunziro angapo (otseguka) a nthawi yayitali omwe odwala matenda ashuga adalandira pioglitazone masabata makumi awiri ndi awiri. Chifukwa mayeso azachipatala safalitsidwa kawirikawiri mwatsatanetsatane, zambiri zomwe zimachokera zimayambiranso kapena zolengedwa.

Mankhwala ndi placebo amafananizidwa ndi kafukufuku wambiri wakhungu wopitilira masabata 26. Kafukufuku wina momwe anthu 408 adatenga nawo gawo adalembedwa kwathunthu. Zotsatirazi zitha kufotokozedwa mwachidule motere: pamtunda kuchokera pa 15 mpaka 45 mg / tsiku, pioglitazone idapangitsa kutsika kwa HbA1c komanso kudya magazi.

Poyerekeza mwachindunji ndi wothandizila wina wodwala matenda amkamwa, chidziwitso chochepa chabe chomwe chilipo: kafukufuku wowunika wa khungu la 26-sabata kawiri ndi odwala 263 adawonetsa kuperewera pang'ono poyerekeza ndi glibenclamide.

Mankhwalawa ali ophatikizidwa m'mimba ndi kuyamwa, komanso mwa ana ndi achinyamata. Pioglitazone imatsutsana kwambiri odwala omwe ali ndi hypersensitivity, matenda a shuga omwe amadalira insulin, kulephera kwa Cardiogenic, hepatopathy wofatsa komanso wodwala matenda ashuga. Mukamamwa mankhwala, muyenera kuyang'anira ntchito ya chiwindi pafupipafupi kuti musathenso kusintha komwe kumachitika kwambiri.

Zotsatira zoyipa

Monga glitazones yonse, pioglitazone imasungabe madzi m'thupi, yomwe imatha kudziwonekera mu mawonekedwe a edema ndi kuchepa magazi; pakachitika kulephera kwa mtima kwaposachedwa, vuto lalikulu limatha - pulmonary edema. Peoglitazone adanenanso kuti amayambitsa kupweteka kwam'mutu, matenda am'mimba kupuma, minofu, kupweteka kwa molumikizana, komanso kukokana kwa mwendo. M'maphunziro a nthawi yayitali, phindu lolemera kwambiri linali 5%, lomwe silimangokhudzana ndi kusungidwa kwamadzi, komanso kuwonjezeka kwa minofu ya adipose.

Pioglitazone monotherapy sikuwoneka kuti limalumikizidwa ndi chiwopsezo chachikulu cha hypoglycemia. Komabe, pioglitazone imakulitsa chiwopsezo cha sulfonylureas kapena insulin, yomwe imawonjezera chiopsezo cha hypoglycemia ndi njira zophatikizira zotere.

Mwa odwala ena, transaminase inakula. Zowonongeka kwa chiwindi zomwe zimawonedwa pakumwa ma glitazones ena sizinapezeke mukamamwa mankhwalawa. Cholesterol chonse chitha kuchuluka, koma HDL ndi LDL sizisintha.

Mu Seputembala 2010, U.S. Food and Drug Administration idalimbikitsa kuyesa mankhwala kuti apewe matenda a khansa ya chikhodzodzo. M'mbuyomu m'maphunziro awiri azachipatala, kuchuluka kwa khansa kumawonedwa ndi mankhwala. Asayansi akuti palibe mgwirizano pakati pa kumwa mankhwalawa ndi khansa.

Mlingo ndi bongo

Pioglitazone amatengedwa kamodzi patsiku. Mlingo woyambayo umalimbikitsa kuyambira 15 mpaka 30 mg / tsiku, mlingo ungathe kuwonjezeka pang'onopang'ono pamilungu ingapo. Popeza troglitazone ndi hepatotoxic, ma enzyme a chiwindi amayenera kuyang'aniridwa nthawi zonse akamamwa mankhwalawa pazifukwa zotetezeka. Pioglitazone sayenera kugwiritsidwa ntchito ngati chizindikiro cha matenda a chiwindi.

Pakadali pano, kudakali zoletsa zambiri pakugwiritsa ntchito zinthu zatsopano komanso zodula izi, chifukwa zovuta ndi maphunzirowa sanaphunziridwe mokwanira.

Kuchita

Palibe mogwirizana. Komabe, kulumikizana kungakhalepo pazinthu zomwe zimalepheretsa kapena kuyambitsa ma enzymes ofunikira kwambiri - CYP2C8 / 9 ndi CYP3A4. Sitikulimbikitsidwa kuphatikiza fluconazole ndi mankhwalawa.

Maganizo a dokotala wodziwa bwino komanso wodwala matenda ashuga.

Pioglitazone ndi mankhwala okwera mtengo omwe amalembedwa kwa odwala omwe ali ndi vuto la metformin.Mankhwalawa amatha kukhala ndi hepatotoxic, chifukwa chake odwala amafunika kuyang'ananso chiwindi ndikuwuza dokotala kusintha kulikonse.

Boris Mikhailovich, katswiri wa matenda ashuga

Anamwa metformin ndi mankhwala ena omwe sanathandize. Kuyambira metformin, m'mimba mwanga mudapweteka tsiku lonse, chifukwa chake ndidakana. Wolemba "pioglar", ndakhala ndikumwa miyezi inayi ndipo ndikumva bwino. Sindikuwona zoyipa.

Mtengo (mu Russian Federation)

Mtengo wa pamwezi wa Pioglar (kuyambira 15 mpaka 45 mg / tsiku) umachokera ku 2000 mpaka 3500 rubles aku Russia. Chifukwa chake, pioglitazone, monga lamulo, ndi zotsika mtengo kuposa rosiglitazone (4-8 mg / tsiku), zomwe zimapanga 2300 mpaka 4000 rubles pamwezi.

Yang'anani! Mankhwala amaperekedwa mosamalitsa malinga ndi zomwe dokotala wakupatsani. Musanagwiritse ntchito, pitani kuchipatala.