Repaglinide (Repaglinide)

Oral hypoglycemic wothandizira. Mwamsanga amachepetsa shuga m'magazi ndikulimbikitsa kutulutsa kwa insulin kuti isagwire ntchito pancreatic β-cell. Limagwirira ntchito limayenderana ndi kuthekera kotchinga njira zotsalira za ATP pamafelemu a β-cell pochita zinthu zina zomwe zimapangitsa kuti maselo azitseguka komanso kutsegulidwa kwa njira za calcium. Zotsatira zake, kuchuluka kwa calcium kumapangitsa kuti insulin itulutsidwe ndi ma cell a β.

Pambuyo pakutenga repaglinide, kuyankha kwa insulinotropic pakudya kwa mphindi 30, komwe kumapangitsa kutsika kwa shuga m'magazi. Pakati pa chakudya, palibe kuwonjezeka kwa insulin. Odwala omwe ali ndi matenda a shuga a mitundu yachiwiri (omwe samadalira insulini), akamamwa mankhwala obwera chifukwa cha 500 μg mpaka 4 mg, amadziwika kuti kuchuluka kwa shuga m'magazi kumadziwika.

Pharmacokinetics

Pambuyo pakulowetsa, repaglinide imatengedwa mwachangu kuchokera kumimba, pomwe Cmax imafikira ola limodzi pambuyo pa utsogoleri, ndiye kuti mlingo wa repaglinide mu plasma umatsika mofulumira ndipo pambuyo maola 4 umatsika kwambiri. Panalibe kusiyana kwakukulu m'magawo a pharmacokinetic a repaglinide pamene amatengedwa musanadye, 15 ndi 30 mphindi musanadye kapena pamimba yopanda kanthu.

Kumanga mapuloteni a Plasma ndi oposa 90%.

Vd ndi 30 L (yomwe imagwirizana ndi kagawidwe kamakina am'madzi).

Repaglinide imangokhala biotransformed mu chiwindi ndikupanga ofooka metabolites. Repaglinide ndi metabolites ake amuchotsa makamaka ndi bile, osachepera 8% - ndi mkodzo (monga metabolites), ochepera 1% - okhala ndi ndowe (zosasinthika). T1 / 2 ili pafupifupi ola limodzi.

Rimage regimen imakhazikitsidwa payekhapayekha, kusankha mlingo kuti mukulitse milingo ya shuga.

Mlingo woyambira wabwino ndi 500 mcg. Kuchulukitsa kwa mankhwalawa kuyenera kuchitidwa osapitilira sabata ziwiri za kudya kwambiri, kutengera magawo a labotale ofooketsa kagayidwe.

Mlingo waukulu: umodzi - 4 mg, tsiku lililonse - 16 mg.

Mukatha kugwiritsa ntchito mankhwala ena a hypoglycemic, mlingo woyambira ndi 1 mg.

Tengani chakudya chachikulu chilichonse. Nthawi yoyenera kumwa mankhwalawa ndi mphindi 15 musanadye, koma angathe kumwa mphindi 30 musanadye kapena nthawi yomweyo musanadye.

Kuyanjana kwa mankhwala osokoneza bongo

Kupititsa patsogolo zotsatira za hypoglycemic za repaglinide ndizotheka kugwiritsa ntchito nthawi imodzi ya ma MA inhibitors, osasankha beta-blockers, zoletsa za ACE, salicylates, NSAIDs, octreotide, anabolic steroids, ethanol.

Kuchepetsa mphamvu ya hypoglycemic ya repaglinide ndikotheka ndikugwiritsira ntchito munthawi yomweyo mankhwala othandizira kulera pakamwa, thiazide diuretics, GCS, danazole, mahomoni a chithokomiro, sympathomimetics (popereka kapena kuletsa mankhwalawa, ndikofunikira kuyang'anira mkhalidwe wa kagayidwe kazakudya).

Pogwiritsa ntchito munthawi yomweyo mankhwala osokoneza bongo omwe amapezeka mu ndulu, mwayi womwe ungathe kuyanjana pakati pawo uyenera kuganiziridwa.

Pokhudzana ndi deta yomwe ikupezeka pa metabolism ya repaglinide ndi CYP3A4 isoenzyme, kuyanjana kwa CYP3A4 inhibitors (ketoconazole, intraconazole, erythromycin, fluconazole, mibefradil), zomwe zikutsogolera kuwonjezeka kwa plasma repaglinide level, ikuyenera kukumbukiridwa. Zoyambitsa CYP3A4 (kuphatikizapo rifampicin, phenytoin), zitha kuchepetsa kupatsirana kwa plaglinide mu plasma. Popeza kuchuluka kwa kupangidwako sikunakhazikitsidwe, kugwiritsa ntchito mobwerezabwereza kwa repaglinide ndi mankhwalawa kumatsutsana.

Mimba komanso kuyamwa

Gwiritsani ntchito pa mimba ndi mkaka wa m`mawere ali contraindicated.

M'maphunziro oyesera, zidapezeka kuti palibe mphamvu ya teratogenic, koma ikagwiritsidwa ntchito pamlingo wambiri m'magawo omaliza a mimbayo, embryotoxicity komanso kusokonezeka kwa miyendo mwa mwana wosabadwayo. Repaglinide imafukusidwa mkaka wa m'mawere.

Zotsatira zoyipa

Kuchokera kumbali ya kagayidwe: kakhudzidwe kagayidwe kazakudya kachulukidwe kachulukidwe ka magazi (pallor, kuchuluka kwa thukuta, matenda, kugona tulo, kunjenjemera), kusinthasintha kwa magazi m'magazi kungayambitse kupenyerera kwakanthawi, makamaka kumayambiriro kwa chithandizo (adanenedwa ochepa odwala ndipo osatero zofunika kuchotsedwa kwa mankhwalawa).

Kuchokera mmimba dongosolo: kupweteka kwam'mimba, kutsegula m'mimba, kusanza, kusanza, kudzimbidwa, zina - kuchuluka kwa michere ya chiwindi.

Thupi lawo siligwirizana: kuyabwa, erythema, urticaria.

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

Contraindication

Type 1 shuga mellitus (wodalira insulini), matenda ashuga a ketoacidosis (kuphatikiza ndi chikomokere), kuvulala kwambiri kwaimpso, kusokonekera kwa chiwindi, kulandira chithandizo chamankhwala limodzi ndi mankhwala omwe amalepheretsa CYP3A4, pakati (kuphatikizapo kukonzekera) , mkaka wa m`mawere, hypersensitivity kuti repaglinide.

Malangizo apadera

Ndi chiwindi kapena matenda a impso, opaleshoni yayikulu, matenda kapena matenda aposachedwa, kuchepa kwa kugwiranso ntchito kwa zotheka kumatha.

Gwiritsani ntchito mosamala odwala omwe ali ndi matenda a impso.

Odwala ofooka kapena odwala omwe amachepetsa zakudya, ayenera kuyambiranso kumwa mankhwalawa. Popewa kuthana ndi hypoglycemic pagulu la odwala, mlingo uyenera kusankhidwa mosamala.

Mikhalidwe yomwe ikukwera ya hypoglycemic nthawi zambiri imakhala yotsogola ndipo imaletseka mosavuta kudya mafuta. Woopsa, zitha kukhala zofunikira / pakubweretsa shuga. Kuchepa kwa kukhazikika kotereku kumatengera mlingo, zakudya mthupi, kulimbitsa thupi, kupsinjika.

Chonde dziwani kuti beta-blockers amatha kufinya zizindikiro za hypoglycemia.

Pa chithandizo, odwala ayenera kupewa kumwa mowa, monga Mowa umatha kukulitsa ndikuwonjezera mphamvu ya hypoglycemic ya repaglinide.

Kukopa pa kuyendetsa magalimoto ndi kayendedwe kazinthu

Poyerekeza ndi kagwiritsidwe ntchito ka ntchito yoyambitsanso, kutha kuyendetsa galimoto kapena kuchita zinthu zina zoopsa kuyenera kuyesedwa.

Pharmacology

Imalepheretsa njira zotsalira za potaziyamu ya ATP mu zimagwira ntchito za beta zogwira ntchito za kanyumba kanyumba, zimayambitsa kukhumudwa komanso kutsegulidwa kwa njira za calcium, kupangitsa insulini kuwonjezera. Kuyankha kwa insulinotropic kumayamba pakadutsa mphindi 30 pambuyo pa ntchito ndipo kumayendetsedwa ndi kuchepa kwa shuga wamagazi pakudya (kuchuluka kwa insulin pakati pa chakudya sikukula).

Poyeserera mu vivo ndipo nyama sizinawululire mutagenic, teratogenic, carcinogenic zotsatira komanso chonde pakubereka.

Kuchita

Beta-blockers, ACE inhibitors, chloramphenicol, osadziwika anticoagulants (coumarin zotumphukira), NSAIDs, probenecid, salicylates, Mao inhibitors, sulfonamides, mowa, anabolic steroid - zimathandizira. Calcium calcium blockers, corticosteroids, okodzetsa (makamaka thiazide), isoniazid, nicotinic acid mu mlingo waukulu, estrogens, kuphatikiza monga gawo la njira yolerera pakamwa, phenothiazines, phenytoin, sympathomimetics, mahomoni a chithokomiro amachepetsa mphamvu.

Bongo

Zizindikiro: hypoglycemia (njala, kumva kutopa ndi kufooka, kupweteka mutu, kusokonezeka, kuda nkhawa, kugona, kusowa tulo, zolakwika, zosintha zofanana ndi zomwe zimawonedwa pakumwa zakumwa zoledzeretsa, kufooketsa chidwi cha chidwi, malankhulidwe ndi masomphenya. nseru, palpitations, kukokana, thukuta, ozizira, etc.).

Chithandizo: ndi hypoglycemia yolimbitsa thupi, popanda zizindikiro zamitsempha ndi kusazindikira - kumwa chakudya (shuga kapena shuga) mkati ndikusintha mlingo kapena zakudya. Mwa mawonekedwe owopsa (kupsinjika, kusazindikira, chikomokere) - mu / pakukhazikitsa njira ya shuga ya 50% yotsatiridwa ndi kulowetsedwa kwa 10% yothetsera kukhalabe ndi shuga wamagazi osachepera 5.5 mmol / L.

Chenjezo la mankhwala a Repaglinide

Gwiritsani ntchito mosamala odwala omwe ali ndi vuto la chiwindi kapena impso. Pa mankhwala, ndikofunikira kuwunika pafupipafupi kuchuluka kwa shuga m'magazi pamimba yopanda kanthu ndikatha kudya, kupindika kwa shuga m'magazi ndi mkodzo. Wodwala ayenera kuchenjezedwa za chiwopsezo cha hypoglycemia chifukwa chophwanya regimen, kudya mokwanira, kuphatikiza mukasala kudya, ndimamwa mowa. Ndi nkhawa yakuthupi komanso yamalingaliro, kusintha kwa mankhwalawa ndikofunikira.

Gwiritsani ntchito mosamala mukamagwira ntchito yoyendetsa magalimoto ndi anthu omwe ntchito yawo imalumikizidwa ndi chidwi chochuluka.

Mlingo

Mapiritsi 0,5 mg, 1 mg, 2 mg

Piritsi limodzi lili

ntchito yogwira - repaglinide 0,5 mg, 1.0 mg, 2.0 mg,

obwera: microcrystalline cellulose, wowonda wa mbatata, calcium hydrogen phosphate, polacryline, povidone K-30, glycerin, poloxamer 188, magnesium kapena calcium stearate, yellow iron oxide (E 172) pa 1 mg imodzi, red iron oxide (E 172) wa 2 mg. .

Mapiritsi ndi oyera kapena pafupifupi oyera (kwa mulingo wa 0,5 mg), kuchokera ku chikasu chowala mpaka chikasu (kwa mulingo wa 1,0 mg), kuchokera ku pinki yopepuka mpaka pinki (kwa mulingo wa 2.0 mg), yozungulira, yokhala ndi biconvex.

Mankhwala

Pharmacokinetics

Repaglinide imatengeka mwachangu kuchokera ku m'mimba, komwe kumayendetsedwa ndi kuwonjezereka kwazomwe zimachitika mu plasma. Kuchuluka kwa repaglinide mu plasma kumatheka mkati mwa ola limodzi pambuyo pa makonzedwe.

Panalibe kusiyana kwakukulu pakati pa pharmacokinetics of repaglinide pamene idatengedwa musanadye, mphindi 15 kapena 30 mphindi musanadye kapena pamimba yopanda kanthu.

The pharmacokinetics of repaglinide imadziwika ndi bioavailability pafupifupi 63% (kusiyanasiyana coefficient (CV) ndi 11%).

M'maphunziro azachipatala, kuphatikiza kwakukulu kwapagulu (60%) ya plasma repaglinide concentration kunawululidwa. Kusiyanasiyana kwapakati pa munthu payekha kumakhala kotsika mpaka pang'ono (35%). Popeza titration wa mlingo wa repaglinide ikuchitika malinga ndi mayendedwe a wodwalayo kulandira chithandizo, mitundu mitundu sizikhudza mphamvu ya mankhwala.

The pharmacokinetics of repaglinide imadziwika ndi gawo lotsika logawa 30 l (malinga ndi momwe amagawidwira mu intracellular fluid), komanso gawo lalikulu lomangiriza mapuloteni a plasma a anthu (oposa 98%).

Pambuyo pofika pazovuta kwambiri (Cmax), zomwe zimapezeka m'madzi a plasma zimachepa kwambiri. Hafu ya moyo wa mankhwala (t½) ndi pafupifupi ola limodzi. Repaglinide imachotsedwa kwathunthu kuchokera mthupi mkati mwa maola 4-6. Repaglinide imapangidwa kotheratu, makamaka ndi CYP2C8 isoenzyme, komanso, ngakhale pang'ono, mwa CYP3A4 isoenzyme, ndipo palibe metabolites omwe ali ndi vuto lalikulu la hypoglycemic adadziwika.

Repaglinide metabolites imachotsedwa makamaka m'matumbo, pomwe 1% ya mankhwalawa imapezeka mu ndowe zosasinthika. Gawo laling'ono (pafupifupi 8%) la mankhwala omwe amaperekedwa amapezeka mumkodzo, makamaka mawonekedwe a metabolites.

Magulu apadera a odwala

Kuwonetsedwa kwa Repaglinide kumachulukitsidwa kwa odwala omwe ali ndi vuto la chiwindi komanso odwala okalamba omwe ali ndi matenda a shuga a 2. Makhalidwe a AUC (SD) atatha kumwa kamodzi pa 2 mg ya mankhwala (4 mg mwa odwala omwe ali ndi vuto la chiwindi) anali 31.4 ng / ml x ola (28.3) mwa odzipereka athanzi, 304.9 ng / ml x ola (228.0 ) mwa odwala omwe ali ndi vuto la chiwindi ndi 117.9 ng / ml x ola (83.8) mwa odwala okalamba omwe ali ndi matenda amtundu wa 2.

Pambuyo masiku 5 chithandizo ndi repaglinide (2 mg x 3 kawiri pa tsiku), odwala kwambiri aimpso kulephera (creatinine chilolezo: 20-39 ml / min) adawonetsa kuwonjezeka kwapawiri-2 kwamaulidwe (AUC) ndi theka-moyo (t1 / 2 ) Poyerekeza ndi odwala omwe ali ndi vuto laimpso.

Mankhwala

Repaglide ® ndi mankhwala amkamwa achilendo. Mofulumira amachepetsa shuga m'magazi ndikulimbikitsa kutulutsa kwa insulin ndi kapamba. Amamangirira ku membala wa β-cell ndi puloteni inayake ya receptor ya mankhwalawa. Izi zimabweretsa kutsekeka kwa njira yolumikizira potaziyamu ya ATP ndi kukokoloka kwa membrane wam' cell, komwe, kumathandizira kutsegulidwa kwa njira za calcium. Kudya kwa calcium mkati mwa -cell kumapangitsa kuti insulin itulutsidwe.

Odwala omwe ali ndi matenda a shuga a mtundu wachiwiri, insulinotropic imawonedwa pakatha mphindi 30 atatha kumwa mankhwalawo. Izi zimapereka kuchepa kwa shuga m'magazi nthawi yonse ya chakudya. Pankhaniyi, kuchuluka kwa plagmaide mu plasma kumatsika msanga, ndipo maola 4 mutatha kumwa mankhwalawa m'magazi a odwala matenda a shuga a 2, kutsika kwa mankhwala kumapezeka.

Kuchita Mwachipatala ndi Chitetezo

Kuchepetsa amadalira shuga m'magazi a shuga kumawonedwa mwa odwala omwe ali ndi matenda a shuga a 2 omwe amapezeka ndi kuchuluka kwa 0,5 mpaka 4 mg. Kafukufuku wachipatala awonetsa kuti repaglinide iyenera kumwedwa musanadye (prerandial dosing).

Zizindikiro zogwiritsidwa ntchito

- lembani matenda ashuga a 2 a shuga ndi kusachita bwino kwa mankhwala othandizira kudya, kuchepa thupi komanso kuchita masewera olimbitsa thupi

- lembani matenda ashuga a 2 omwe amaphatikizidwa ndi metformin pazochitika zomwe sizingatheke kukwaniritsa kuyendetsa bwino glycemic pogwiritsa ntchito metformin monotherapy.

Therapy iyenera kutumikiridwa ngati chida chowonjezera chothandizira kudya komanso kuchita zolimbitsa thupi kuti muchepetse kuchuluka kwa shuga m'magazi.

Mlingo ndi makonzedwe

Repaglinide ndi mankhwala okhazikika. Kusankha kwa dose kumachitika payekhapayekha kukhathamiritsa kuwongolera kwa glycemic. Kuphatikiza pa kuwonetsetsa momwe wodwalayo amayang'anira magazi ndi mkodzo m'magazi ake, kuwunika kwa shuga kuyenera kuchitidwa ndi dokotala kuti adziwe mlingo wofunikira kwambiri wa wodwalayo. Kuphatikizika kwa glycosylated hemoglobin ndikuwonetsanso momwe wodwala amayankhira chithandizo. Kuwunika kwa nthawi yayitali ndende ya glucose ndikofunikira kuti muzindikire kuchepa kwa magazi m'magazi poyambira wodwalayo chifukwa cha kuchuluka kwa mankhwalawa (ndiko kuti, wodwalayo ali ndi "kukana kwakukulu"), komanso kudziwa kufooka kwa mayankho a hypoglycemic (ndiye kuti, wodwalayo ali ndi "kukana kwachiwiri").

Kuperekera kwakanthawi kochepa kungakhale kokwanira panthawi yochepetsetsa yolamulidwa ndi odwala omwe ali ndi matenda a shuga a 2, nthawi zambiri amakhala zakudya zabwino.

Mlingo wa mankhwalawa umatsimikiziridwa ndi dokotala kutengera kuchuluka kwa shuga m'magazi.

Kwa odwala omwe sanalandirepo mankhwala ena amkamwa a hypoglycemic, njira yokhayo yoyamba isanadye ndi 0,5 mg. Kusintha kwa Mlingo kumachitika kamodzi pa sabata kapena kamodzi pa masabata awiri (poyang'ana kwambiri kuchuluka kwa shuga m'magazi monga chisonyezo cha kuyankha kwa mankhwala).Ngati wodwalayo atembenuka kuti atenge njira ina yothandizira pakamwa ya hypoglycemic kuti athandizidwe ndi Repaglid ®, ndiye kuti mlingo woyambirira woyenera musanadye chakudya chachikulu chilichonse chikhale 1 mg.

Mulingo wovomerezeka umodzi musanadye chakudya chachikulu ndi 4 mg. Mankhwala okwanira tsiku lililonse sayenera kupitirira 16 mg.

Kafukufuku wachipatala kwa odwala omwe ali ndi zaka zopitilira 75 sanachitike.

Kuwonongeka kwa impso sikuti kumakhudzanso chimbudzi. 8% ya omwe amatenga muyezo umodzi wa repaglinide amamuchotsetsanso impso ndipo chiwonetsero chonse cha plasma kwa odwala omwe ali ndi vuto la aimpso amachepetsa. Chifukwa chakuti kumva kwa insulin kwa odwala omwe ali ndi matenda ashuga kumawonjezereka ndi kulephera kwa aimpso, kusamala kuyenera kuchitidwa pakusankha Mlingo mwa odwala.

Kafukufuku wachipatala kwa odwala omwe ali ndi vuto la chiwindi sanachitidwe.

Odwala ovutika komanso ofooka

Odwala ofooka komanso opsinjika, mulingo woyenera komanso wowonjezera uyenera kukhala wosasangalatsa. Chisamaliro chiyenera kuthandizidwa posankha milingo kuti musatulutse hypoglycemia.

Odwala omwe adalandiranso mankhwala ena amkamwa a hypoglycemic

Kutumiza kwa odwala omwe ali ndi mankhwalawa ndi mankhwala ena amkamwa a hypoglycemic kuthandizira ndi repaglinide kungachitike nthawi yomweyo. Komabe, ubale womwe ulipo pakati pa mlingo wa repaglinide ndi mlingo wa mankhwala ena a hypoglycemic sunawululidwe. Mlingo woyambira wabwino kwambiri kwa odwala omwe amasinthidwanso ndikuwonjezera 1 mg musanadye chakudya chachikulu chilichonse.

Repaglinide imatha kutumikiridwa limodzi ndi metformin ngati pakuyang'anira kuwunika kwa shuga m'magazi a metformin monotherapy. Pankhaniyi, mlingo wa metformin umasungidwa, ndipo repaglinide imawonjezeredwa ngati mankhwala ena. Mlingo woyamba wa repaglinide ndi 0,5 mg wambiri musanadye. Kusankhidwa kwa Mlingo uyenera kupangidwa molingana ndi mulingo wa glucose m'magazi monga monotherapy.

Kuchita bwino ndi chitetezo cha mankhwala omwe amakhalanso ndi zaka 18 sizinafufuzidwe. Palibe zambiri zomwe zilipo.

Repaglide ® iyenera kumwedwa musanadye chakudya chachikulu (kuphatikizapo Prerandial). Mlingo nthawi zambiri umatengedwa pakatha mphindi 15 mutatha kudya, komabe, nthawi ino imatha kusiyanasiyana ndi mphindi 30 chakudya chisanafike (kuphatikizapo 2.3 ndi zakudya 4 patsiku). Odwala akulumphira zakudya (kapena ndi zina zowonjezera) ayenera kudziwitsidwa za kudumphadumpha (kapena kuwonjezera) mlingo wokhudzana ndi chakudyacho.