Mankhwala Baeta: ndemanga za akatswiri ndi wopanga, mtengo

Mankhwala ndi mtundu 2 matenda a shuga kuti awonjezere mankhwala ena ku:

• khalimon
• metformin
• zotengera sulfonylurea,
• kuphatikiza kwa sulfonylurea, metformin ndi zotumphukira,
• kuphatikiza kwa thiazolidinedione ndi metformin,
• kapena pakalibe kuyendetsa bwino glycemic.

Mlingo

Bayeta imaperekedwa mwachangu ku ntchafu, kutsogolo kapena pamimba. Mlingo woyambirira ndi 5 mcg. Lowani 2 kawiri patsiku pafupifupi ola limodzi musanadye chakudya cham'mawa komanso chakudya chamadzulo. Mukatha kudya, mankhwalawa sayenera kuperekedwa.

Ngati wodwala pazifukwa zina adumpha makina a mankhwalawo, majekeseni ena amapezeka osasinthika. Pakatha mwezi umodzi chithandizo, muyeso woyamba wa mankhwalawa uyenera kuchuluka mpaka 10 mcg.

Ndi makonzedwe apakati pa Bayet omwe ali ndi thiazolidinedione, metformin, kapena kuphatikiza kwa mankhwalawa, mlingo woyambirira wa thiazolidinedione kapena metformin sungasinthidwe.

Ngati mugwiritsa ntchito kuphatikiza kwa Baeta ndi zotumphukira za sulfonylurea (kuti muchepetse chiopsezo cha hypoglycemia), mungafunike kuchepetsa mlingo wa zotumphukira za sulfonylurea.

Zolemba ntchito

• Mankhwala sayenera kuperekedwa pambuyo chakudya,
• kuyambitsa kwa mankhwala IM kapena IV osavomerezeka,
• mankhwalawa sayenera kugwiritsidwa ntchito ngati njira yachepetsedwa kapena kwamtambo,
• Bayetu sayenera kuperekedwa ngati tinthu tating'onoting'ono tapezeka mu yankho.
• motsutsana ndi maziko a mankhwala a exenatide, kupanga antibody ndikotheka.

Zofunika! Odwala ambiri omwe thupi lawo limatulutsa ma antibodies otere, titer inachepa ndipo chithandizo chanakhalabe chochepa kwa milungu 82 pomwe chithandizo chimapitilira. Komabe, kupezeka kwa antibodies sikumakhudza mitundu ndi pafupipafupi pazotsatira zoyipa zomwe zapezeka.

Dokotala wopezekapo ayenera kudziwitsa wodwala wake kuti kuchiza ndi Bayeta kumapangitsa kuti munthu asakhale ndi chidwi chofuna kudya, komanso thupi. Ichi ndi mtengo wotsika bwino poyerekeza ndi momwe mankhwalawo amathandizira.

Poyeserera koyeserera komwe kunachitika pa makoswe ndi mbewa ndikutulutsa magazi pakhungu ndi jakisoni exenatide, sikunapezeke.

Mlingo wa 128 nthawi yomwe anthu amayesedwa ndi mbewa, makoswe amawonetsa kuchuluka (popanda chiwopsezo chilichonse) cha adenomas a chithokomiro C.

Asayansi amati izi zimachulukitsa nthawi yayitali kwambiri ya nyama yoyesera yolandila exenatide. Pafupipafupi, komabe pakhala kuphwanyidwa kwa impso. Zinaphatikizaponso

• kukula kwa aimpso kulephera,
• kuchuluka seramu creatinine,
• kuchuluka kwa nthawi ya pachimake komanso matenda aimpso kulephera, komwe nthawi zambiri kumafunikira hemodialysis.

Zina mwazowonekera izi zimapezeka mwa odwala omwe amamwa mankhwala amodzi kapena angapo nthawi imodzi omwe amakhudza kagayidwe kamadzi, ntchito yaimpso, kapena kusintha kwina kwa pathological kunachitika.

Mankhwala ophatikizira anali ndi NSAIDs, ACE inhibitors, ndi okodzetsa. Mukamapereka mankhwala othandizira ndikuchotsa mankhwalawo, zomwe mwina zinali zomwe zimayambitsa matenda, mawonekedwe a impso adabwezeretseka.

Pambuyo pochita maphunziro azachipatala komanso a preclinical, exenatide sanawone umboni wa nephrotoxicity yake yachindunji. Poyerekeza ndi momwe agwiritsire ntchito mankhwala a Bayeta, milandu yovuta kwambiri ya kapamba yazindikirika.

Chonde dziwani: Odwala ayenera kudziwa zizindikiro za kapamba kapamba. Mukamapereka mankhwala othandizira, kuchiritsa kwachimbudzi kumachitika.

Asanapitilize ndi jekeseni la Bayeta, wodwalayo awerenge malangizo omwe aphatikizidwa ogwiritsa ntchito cholembera, mtengo umasonyezedwanso pamenepo.

Contraindication

1. Kupezeka kwa matenda ashuga ketoacidosis.
2. Mtundu woyamba wa shuga.
3. Mimba
4. Kupezeka kwa matenda am'mimba kwambiri.
5. Kulephera kwakukulu kwaimpso.
6. Kuyamwitsa.
7. Zaka mpaka 18.
8. Hypersensitivity pamagawo a mankhwala.

Mimba komanso Kuyamwitsa

M'magawo onse awiriwa, mankhwala amatsutsana. Mtengo wa malingaliro achinyengo pazolimbikitsazi ukhoza kukhala wokwera kwambiri. Amadziwika kuti zinthu zambiri zamankhwala zimakhumudwitsa kukula kwa mwana wosabadwayo.

Mayi wonyalanyazidwa kapena wopanda nzeru amatsogolera kubadwa kwa mwana wosabadwa. Pafupifupi mankhwala onse amalowa mthupi la mwana ndi mkaka wa amayi, motero magulu awa odwala ayenera kusamala ndi mankhwalawa.

Monotherapy

Zotsatira zoyipa zomwe zimawonedwa mwa odwala koposa kamodzi zidalembedwa motere:

Zomwe zimachitika:

• Kuyabwa nthawi zambiri kumachitika m'malo a jakisoni.
• Pafupipafupi, redness ndi zotupa.

Pa gawo la dongosolo logaya chakudya, mawonetsedwe otsatirawa nthawi zambiri amapezeka:

Mitsempha yapakati ya m'magazi nthawi zambiri imakumana ndi chizungulire. Ngati tiyerekeza mankhwala a Bayeta ndi placebo, ndiye kuti kuchuluka kwa zochitika za hypoglycemia pamankhwala omwe afotokozedwawo kumakhala kwakukulu ndi 4%. Kukula kwa ma episode a hypoglycemia amadziwika ngati ofatsa kapena odziletsa.

Kuphatikiza mankhwala

Zochitika zoyipa zomwe zimawonedwa kwa odwala kopitilira kamodzi ndi chithandizo cha mankhwala ophatikizika ndizofanana ndi omwe ali ndi monotherapy (onani tebulo pamwambapa).

Dongosolo la chimbudzi limayankha:

1. Nthawi zambiri: kusowa kwa chakudya, nseru, kusanza, kutsegula m'mimba, gastroesophageal Reflux, dyspepsia.
2. Nthawi zambiri: kumatulutsa ndi kupweteka kwam'mimba, kudzimbidwa, kuyereketsa, kuphwanya, kusweka kwa zotengeka zamkati.
3. Nthawi zambiri: pachimake kapamba.

Nthawi zambiri, kunyansidwa kwamphamvu kapena kufooka mwamphamvu kumawonedwa. Imadalira mlingo ndipo imatsika pakapita nthawi popanda kukhudza zochita za tsiku ndi tsiku.

Mitsempha yapakati ya m'magazi nthawi zambiri imakumana ndi mutu komanso chizungulire, kawirikawiri ndi kugona.

Kumbali ya endocrine system, hypoglycemia imawonedwa kwambiri ngati exenatide ikuphatikizidwa ndi zotumphukira za sulfonylurea. Kutengera izi, ndikofunikira kuwunika kuchuluka kwa zotumphukira za sulfonylurea ndikuwachepetsa ndi chiwopsezo cha hypoglycemia.

Mitundu yambiri ya hypoglycemic mu kukula imadziwika kuti ndi yofatsa komanso yodziletsa. Mutha kusiya izi pokhapokha pogwiritsa ntchito chakudya. Kumbali ya kagayidwe, mukamamwa mankhwala a Bayeta, Hyperhidrosis imatha kuonedwa, nthawi zambiri kusowa kwamadzi komwe kumachitika chifukwa cha kusanza kapena kutsegula m'mimba.

Kwamikodzo dongosolo kawirikawiri amakumana ndi pachimake aimpso kulephera komanso zovuta matenda.

Ndemanga zikuwonetsa kuti thupi siligwirizana kwenikweni. Izi zitha kukhala zowonetsera edema kapena anaphylactic.

Zomwe zimachitika pakadutsa jakisoni wa exenatide zimaphatikizapo zotupa, redness, ndi kuyabwa pamalowo jakisoni.

Pali malingaliro a milandu ya kuchuluka kwa erythrocyte sedimentation rate (ESR). Izi ndizotheka ngati escinate idagwiritsidwa ntchito nthawi yomweyo ndi warfarin. Mawonetseredwe oterewa nthawi zina amatha kutsagana ndi magazi.

Kwenikweni, zotsatirapo zake zinali zochepa kapena zolimbitsa thupi, zomwe sizinafune kusiya chithandizo.

Pharmacology

Pharmacological kanthu - hypoglycemic, incretinomimetic.

Ma insretins, monga glucagon-like peptide-1 (GLP-1), amasintha ntchito ya maselo a beta, amalimbikitsa secretion wodalira glucose, kupondereza mosabisa mozama kuteteza glucagon ndikuchepetsa m'matumbo atalowetsa magazi ambiri kuchokera m'matumbo. Exenatide ndi mphamvu ya insretin mimetic yomwe imathandizira secretion ya glucose yomwe imadalira shuga ndipo imakhala ndi zotsatira zina za hypoglycemic zomwe zimayambira ma incretins, zomwe zimapangitsa kuti glycemic control mu odwala a mtundu wa 2 shuga.

Mndandanda wa amino acid wa exenatide pang'ono umagwirizana ndi mndandanda wa anthu GLP-1. Exenatide yawonetsedwa kuti imangiriza ndikuyambitsa zolimbitsa thupi za GLP-1 mwa anthu mu vitro, zomwe zimapangitsa kuti shuga ayambe kudalira glucose komanso, mu vivo, pobisalira kwa insulin kuchokera ku maselo a pancreatic beta ndikuchita nawo cyclic AMP ndi / kapena njira zina zowonetsera ma intcacellular.

Exenatide imathandizira kuwongolera kwa glycemic mwa odwala omwe ali ndi matenda a shuga a 2 kudzera m'njira zingapo.

M'mikhalidwe ya hyperglycemic, exenatide imakulitsa katulutsidwe wama shuga a insulin kuchokera kuma cell a pancreatic beta. Katemera wa insuliniyu amathera pomwe kuchuluka kwa glucose m'magazi kumachepera ndipo kumayandikira mwachizolowezi, potero kumachepetsa chiopsezo cha hypoglycemia.

Kubisirana kwa insulin mphindi 10 zoyambirira, komwe kumadziwika kuti "gawo loyamba la mayankho a insulin", kulibe odwala omwe ali ndi matenda a mtundu wa 2. Kuphatikizanso, kutayika kwa gawo loyambirira la mayankho a insulin ndiko kusokonezeka koyambirira kwa ntchito ya cell ya beta mu mtundu wa 2 shuga. kapena kumakulitsa kwambiri gawo loyamba ndi lachiwiri la yankho la insulin mwa odwala omwe ali ndi matenda a shuga a 2.

Odwala ndi mtundu 2 matenda a shuga mellitus motsutsana maziko a hyperglycemia, makonzedwe a exenatide amachepetsa kwambiri secretion wa glucagon. Komabe, exenatide sichimasokoneza mayankho abwinobwino a glucagon ku hypoglycemia.

Zinawonetsedwa kuti kuyang'anira exenatide kumayambitsa kutsika kwa kudya komanso kuchepa kwa chakudya (zonse nyama ndi mwa anthu).

Odwala omwe ali ndi mtundu wachiwiri wa matenda a shuga, mankhwalawa a exenatide akuphatikizidwa ndi metformin ndi / kapena sulfonylurea kukonzekera kumayambitsa kutsika kwa glucose wamagazi, postprandial magazi glucose, ndi glycosylated hemoglobin index (HbA1c), potero kukonza kuwongolera kwa glycemic mwa odwala.

Carcinogenicity, mutagenicity, zimabweretsa chonde

Pakufufuza kwa carcinogenicity ya exenatide mu mbewa ndi makoswe, ndi sc makonzedwe a 18, 70 ndi 250 μg / kg / tsiku, kuchuluka kwamankhwala mu C-cell chithokomiro adenomas popanda zisonyezo zakuda mu makoswe azimayi adadziwika konsekonse , 22 ndi 130 kwambiri kuposa MPD mwa anthu). Makoswe, makonzedwe omwewo sanasonyeze kuwonongeka kwa mtima.

Mutagenic ndi clastogenic zotsatira za exenatide panthawi zingapo zoyesa sizinapezeke.

Mu maphunziro a chonde mu mbewa, mwa akazi omwe amalandira kuchuluka kwa 6, 68 kapena 760 mcg / kg / tsiku, kuyambira pakadutsa masabata awiri asanakwane ndipo mkati mwa masiku 7 ali ndi pakati, sizinawakhudze mwana wosabadwayo pamlingo mpaka mpaka 760 mcg / kg / tsiku (kuwonetsedwa mwadongosolo kuli mpaka 390 kuposa MPRD - 20 mcg / tsiku, kuwerengetsa ndi AUC).

Zogulitsa. Pambuyo pakuyang'anira kwa exenatide muyezo wa 10 μg kwa odwala omwe ali ndi matenda a shuga 2, exenatide imatenga msanga, Cmax (211 pg / ml) imatheka pambuyo pa maola 2.1. AUCo-inf ndi 1036 pg · h / ml. Kuwonetsedwa kwa Exenatide (AUC) kumawonjezeka molingana ndi mlingo womwe umapezeka mu mlingo kuchokera pa 5 mpaka 10 μg, pomwe palibe kuchuluka kwa Cmax. Zomwezi zimawonedwa ndi subcutaneous makonzedwe a exenatide pamimba, ntchafu kapena dzanja.

Kugawa. Vd ya exenatide pambuyo pa sc imodzi imodzi ndi 28.3 L.

Kutetemera ndi chimbudzi. Imapukusidwa makamaka ndi kusefera kwa glomerular komwe kumatsitsidwa ndi kuwonongeka kwa proteinolytic. Chilolezo cha Exenatide ndi 9.1 l / h. T1 / 2 yotsiriza ndi maola 2.4. Makhalidwe awa a pharmacokinetic a exenatide ndi mlingo wodziyimira pawokha. Miyezo yoyeserera ya exenatide imatsimikiziridwa pafupifupi maola 10 mutatha dosing.

Pharmacokinetics mu milandu yapadera yamankhwala

Matenda aimpso. Odwala omwe ali ndi vuto lochepa kapena aimpso (Cl creatinine 30-80 ml / min), kukhudzana kwa exenatide sikunasiyane kwambiri ndi kwa odwala omwe ali ndi vuto laimpso. Komabe, mwa odwala omwe ali ndi vuto loti-a impso amalephera kudikirira dialysis, kuwonekera kwake kunali kokwanira 3.37 kuposa kuposa mitu yathanzi.

Kuwonongeka kwa chiwindi. Kafukufuku wa Pharmacokinetics mwa odwala omwe ali ndi vuto la chiwindi kapena chovuta chotere sanachitike.

Mtundu. Ma pharmacokinetics a exenatide mwa oyimira mafuko osiyanasiyana samasintha.

Thupi Mass Index (BMI). Kuwunikira kwa pharmacokinetic kwa odwala omwe ali ndi BMI ya ≥30 kg / m2 ndi Exenatide

Type 2 shuga mellitus monga njira yowonjezera pochizira ndi metformin, sulfonylurea derivative, thiazolidinedione, kuphatikiza kwa metformin ndi zotumphukira za sulfonylurea, kapena kuphatikiza kwa metformin ndi thiazolidinedione ngati simungathe kuyendetsa bwino glycemic.

Zotsatira zoyipa za mankhwala Exenatide

Gwiritsani ntchito metformin komanso / kapena sulfonylurea

Gome limawonetsa zoyipa (kupatula hypoglycemia) zomwe zimachitika pafupipafupi ndi ≥5% ndipo zidapitilira placebo zotchulidwa m'mayesero atatu owongoleredwa a masabata 30 kuphatikiza metformin ndi / kapena suffonylurea.

Zotsatira zoyipa zomwe zimachitika kawirikawiri> 1%, koma mogwirizana

Exenatide iyenera kugwiritsidwa ntchito mosamala odwala omwe amamwa pakamwa mankhwala omwe amafunikira kuti ayambe kuthamanga m'matumbo, amatha kuchedwetsa kutaya kwa m'mimba. Odwala ayenera kulangizidwa kuti amwe mankhwala amkamwa, momwe zimadalira mphamvu zawo (mwachitsanzo, mankhwala a antibayotiki), osachepera ola limodzi musanayambitse exenatide. Ngati mankhwalawa amayenera kumwa ndi chakudya, ndiye kuti ayenera kumwedwa nthawi yomwe chakudya sichikuperekedwa.

Digoxin. Ndi makonzedwe omwewo a digoxin (pa mlingo wa 0,25 mg 1 nthawi / tsiku) ndi exenatide (10 μg 2 kawiri pa tsiku), Cmax ya digoxin imatsika ndi 17%, ndipo Tmax imawonjezeka ndi maola 2,5. Komabe, kuchuluka kwathunthu kwa pharmacokinetic (AUC) mu boma lofanana silisintha.

Lovastatin. Ndi muyezo umodzi wa lovastatin (40 mg) pakumatenga exenatide (10 μg 2 kawiri patsiku), AUC ndi Cmax ya lovastatin amatsika pafupifupi 40 ndi 28%, motero, ndipo Tmax adakula ndi maola 4. Mu kafukufuku wazachipatala wazama 30, ma exenatide adaperekedwa kwa odwala kulandira kale HMG-CoA reductase inhibitors sikunayendetsedwe ndi kusintha kwa kapangidwe ka magazi ka lipid.

Lisinopril. Odwala omwe ali ndi vuto lochepa kwambiri kapena lochepa kwambiri la okhazikika mwa 5-5 mg / tsiku, exenatide sanasinthe AUC ndi Cmax ya lisinopril pakufanana. Tmax of lisinopril pa equilibrium idakwera ndi maola 2. Panalibe kusintha pazomwe zikuwonetsa pafupifupi SBP ndi DBP tsiku lililonse.

Warfarin. M'mayeso azachipatala olamulidwa mwa odzipereka athanzi, zidadziwika kuti ndikukhazikitsa warfarin patatha mphindi 30 kuchokera ku exenatide, Tmax ya warfarin inachuluka pafupifupi maola 2. Palibe kusintha kwakukuru ku Cmax ndi AUC. Panthawi yowonera pambuyo pakutsatsa, milandu ingapo yowonjezereka ya INR imanenedwa, nthawi zina imayendera limodzi ndi magazi munthawi yomweyo kugwiritsa ntchito exenatide ndi warfarin (kuyang'anira PV ndikofunikira, makamaka kumayambiriro kwa chithandizo komanso pamene mlingo umasinthidwa).

Kugwiritsa ntchito exenatide kuphatikiza ndi insulin, D-phenylalanine, zotumphukira za meglitinides kapena alpha-glucosidase sizinaphunzire.

Mosamala Exenatide

Chifukwa chakuti pafupipafupi hypoglycemia imachulukana limodzi ndi kuphatikiza kwa exenatide ndi zotumphukira za sulfonylurea, ndikofunikira kupatsa kuchepetsedwa kwa mlingo wa zotengera za sulfonylurea ndi chiopsezo chowonjezeka cha hypoglycemia. Magawo ambiri a hypoglycemia mwamphamvu anali ofatsa kapena olimbitsa ndipo anali kuyimitsidwa ndi kudya kwa pakamwa.

Ndiwosavomerezeka mu / mu kapena / m kayendetsedwe ka mankhwalawa.

Munthawi yakuwonetsa pambuyo pakutsatsa, kawirikawiri milandu yokhudzana ndi kupweteka kwa kapamba kwa odwala omwe amatenga exenatide adadziwika. Odwala ayenera kudziwitsidwa kuti kupweteka kwakitali m'mimba, komwe kumatha kutsagana ndi kusanza, ndiye chizindikiro cha kapamba. Ngati mukukayikira kuti apanga pancreatitis, exenatide kapena mankhwala ena omwe akuwoneka kuti akuyenera kuyikiridwa, ziyeso zotsimikizika ziyenera kuchitika ndipo chithandizo choyenera chiyenera kuyambitsidwa. Ngati matenda a kapamba amatsimikiziridwa, kuyambiranso kwa chithandizo ndi exenatide sikulimbikitsidwa mtsogolo.

Munthawi yakuwonetsa pambuyo pakutsatsa, milandu yovuta yaimpso idadziwika, kuphatikizapo kuchuluka kwa serum creatinine, kukulira mu kulephera kwa impso, kulephera kwaimpso, nthawi zina kumafunikira hemodialysis. Zina mwazomwezi zimadziwika ndi odwala omwe amamwa mankhwala amodzi kapena zingapo ndi njira yodziwika yogwiritsira ntchito impso ndi / kapena odwala omwe anali ndi mseru, kusanza komanso / kapena kutsekula m'mimba ndi / popanda hydration, akumwa mankhwala, kuphatikiza . ACE inhibitors, NSAIDs, okodzetsa. Kuwonongeka kwaimpso kunasinthidwanso ndikuchiritsa komanso kuchotsa mankhwala, zomwe zingayambitse matenda aimpso, kuphatikizapo exenatide. Mu maphunziro oyamba komanso zamankhwala, exenatide sanawone mwachindunji nephrotoxicity.

Ma antibodies kuti exenatide awoneke nthawi ya mankhwala ndi exenatide.

Odwala ayenera kudziwitsidwa kuti chithandizo chokhala ndi exenatide chingayambitse kuchepa kwa chilimbikitso ndi / kapena kulemera kwa thupi komanso kuti chifukwa cha izi palibe chifukwa chosinthira njira.

Nkhani Zogwirizana

• Exenatide (exenat> Ntchito Zofunsa

Mankhwalawa amathandizidwa ndi mankhwalawa kumtunda kapena pakati pa phewa, ntchafu, komanso m'mimba. Monga lamulo, tikulimbikitsidwa kusinthana mawebusayiti kuti tipewe kupanga ma sublomaneous conglomerates.

Kubaya kuyenera kuchitidwa mogwirizana ndi malamulo onse ogwiritsira ntchito cholembera. Mankhwala ayenera kuperekedwa kwa ola limodzi pamaso waukulu chakudya pafupipafupi 6 maola.

Exenatide sangathe kusakanikirana ndi mitundu ina ya mlingo, yomwe ingapewe kukula kosakhudzidwa kosayenera.

Kuphatikizidwa kwa BAETA

Njira yothetsera utsogoleri wa sc ndi yopanda utoto, wowonekera.

Omwe amathandizira: sodium acetate trihydrate, glacial acetic acid, mannitol, metacresol, madzi a ndi.

1.2 ml - ma syringe pensulo (1) - mapaketi a makatoni (1).
2.4 ml - zolembera za syringe (1) - mapaketi a makatoni (1).

Hypoglycemic mankhwala. Glucagon-ngati Peptide Receptor Agonist

Hypoglycemic mankhwala. Exenatide (Exendin-4) ndi incretin mimetic ndipo ndi 39-amino acid amidopeptide. Ma insretins, monga glucagon-peptide-1 (GLP-1), amalimbikitsa kuteteza shuga m'magazi, kumapangitsanso ntchito ya β-cell, kupondereza kusungunuka kwa glucagon ndikuchepetsa m'matumbo atalowetsa magazi ambiri kuchokera m'matumbo. Exenatide ndi mphamvu ya insretin mimetic yomwe imathandizira secretion ya glucose yomwe imadalira shuga ndipo imakhala ndi zotsatira zina za hypoglycemic zomwe zimayambira ma incretins, zomwe zimapangitsa kuti glycemic control mu odwala a mtundu wa 2 shuga.

Mndandanda wa amino acid wokhudzana ndi exenatide pang'ono umafanana ndi kufanana kwa anthu a GLP-1, chifukwa chomwe chimamangiriza ndikuyambitsa zolandilira za GLP-1 mwa anthu, zomwe zimapangitsa kuti chiwonetsero cha glucose chodalira komanso kutulutsa kwa insulini kuchokera ku ma cell a pancreatic ndi / kapena ma intracellular signation njira. Exenatide imathandizira kutulutsa kwa insulin kuchokera ku β-cell pamaso pamagulu okwanira a glucose.

Exenatide amasiyana mu kapangidwe ka mankhwala ndi zochita zamapangidwe a insulin, zotumphukira za sulfonylurea, zotumphukira za D-phenylalanine ndi meglitinides, biguanides, thiazolidinediones ndi alpha-glucosidase inhibitors.

Exenatide imathandizira kuwongolera kwa glycemic mwa odwala omwe ali ndi matenda a shuga a 2 chifukwa cha njira zotsatirazi.

M'mikhalidwe ya hyperglycemic, exenatide imakulitsa katulutsidwe kamatenda a glucose kutengera ma cell a pancreatic ic-cell. Katemera wa insuliniyu amathera pomwe kuchuluka kwa glucose m'magazi kumachepera ndipo kumayandikira mwachizolowezi, potero kumachepetsa chiopsezo cha hypoglycemia.

Katemera wa insulin mkati mwa mphindi 10 zoyambirira (poyankha kuchuluka kwa glycemia), yemwe amadziwika kuti "gawo loyamba la mayankho a insulin", sapezeka kwenikweni kwa odwala omwe ali ndi matenda a shuga a 2. Kuphatikiza apo, kutayika kwa gawo loyamba la mayankho a insulin ndikusokonezeka koyambirira kwa ntchito ya β-cell mu mtundu 2 wa matenda ashuga. Kukhazikitsidwa kwa exenatide kumabwezeretsa kapena kumakulitsa kwambiri magawo oyamba ndi achiwiri a kuyankha kwa insulin odwala omwe ali ndi matenda a shuga a 2.

Odwala ndi mtundu 2 matenda a shuga mellitus motsutsana maziko a hyperglycemia, makonzedwe a exenatide amachepetsa kwambiri secretion wa glucagon. Komabe, exenatide sichimasokoneza mayankho abwinobwino a glucagon ku hypoglycemia.

Zinawonetsedwa kuti kukhazikika kwa exenatide kumayambitsa kutsika kwa kudya komanso kuchepa kwa chakudya, kumalepheretsa matumbo, omwe amatsogolera pakuchepa kwake.

Odwala omwe ali ndi mtundu wachiwiri wa matenda osokoneza bongo a mellitus, exenatide mankhwala osakanikirana ndi metformin, thiazolidinedione ndi / kapena sulfonylurea kukonzekera kumayambitsa kutsika kwa shuga wamagazi, postpandial glucose, komanso HbA 1c, potero kuwongolera kayendedwe ka glycemic mwa odwala.

Pambuyo pa s / c makonzedwe a exenatide pa mlingo wa 10 μg kwa odwala omwe ali ndi matenda a shuga 2, exenatide imatengedwa mwachangu ndikufika pafupifupi max C pambuyo pa maola 2.1, omwe ndi 211 pg / ml, AUC o-inf ndi 1036 pg × h / ml. Tivumbulutsidwa ndi exenatide, AUC imawonjezeka molingana ndi kuchuluka kwa mlingo kuchokera pa 5 μg mpaka 10 μg, pomwe palibe kuwonjezeka kwa C max. Zomwezi zimawonedwa ndi subcutaneous makonzedwe a exenatide pamimba, ntchafu kapena dzanja.

V d wa exenatide pambuyo sc makonzedwe ndi 28.3 L.

Kutetemera ndi chimbudzi

Exenatide imapangidwa makamaka ndi kusefera kwa glomerular kutsatiridwa ndi kuwonongeka kwa proteinolytic. Chilolezo cha Exenatide ndi 9.1 l / h. T 1/2 yotsiriza ndi maola 2.4. Makhalidwe awa a pharmacokinetic a exenatide ndi mlingo wodziyimira pawokha. Miyezo yoyeserera ya exenatide imatsimikiziridwa pafupifupi maola 10 mutatha dosing.

Pharmacokinetics mu milandu yapadera yamankhwala

Odwala omwe ali ndi vuto lowonongeka la impso (CC 30-80 ml / min), chilolezo cha exenatide sichosiyana kwambiri ndi chilolezo cha odwala omwe ali ndi vuto laimpso, chifukwa chake, kusintha kwa mankhwalawa sikofunikira. Komabe, mwa odwala omwe ali ndi vuto la aimpso omwe amalephera kudutsa dialysis, chilolezo chotsika chimatsitsidwa ku 0,9 l / h (poyerekeza ndi 9.1 l / h m'maphunziro athanzi).

Popeza exenatide imakhala yotulutsidwa ndi impso, akukhulupirira kuti chiwindi ntchito sichitha kusintha kuchuluka kwa magazi m'magazi.

M'badwo sizikhudza mawonekedwe a pharmacokinetic a exenatide. Chifukwa chake, odwala okalamba sayenera kuchita kusintha kwa mlingo.

Ma pharmacokinetics a exenatide mwa ana osakwana zaka 12 sanaphunzire.

Mu kafukufuku wa pharmacokinetic mu achinyamata a zaka 12 mpaka 16 zokhala ndi matenda a shuga 2, pomwe exenatide adalembedwa pa mlingo wa 5 μg, magawo a pharmacokinetic anali ofanana ndi akulu.

Palibe kusiyana kwakanema pakati pa amuna ndi akazi omwe ali mu pharmacokinetics of exenatide.

Ma pharmacokinetics a exenatide mwa oyimira mafuko osiyanasiyana samasintha. Kusintha kwa mankhwalawa kutengera mtundu wa makolo sikofunikira.

Palibenso kulumikizana kowoneka bwino pakati pa body index index (BMI) ndi exenatide pharmacokinetics. Kusintha kwa Mlingo woyambira BMI sikofunikira.

Zizindikiro BAETA

Zambiri zomwe BAETA imathandizira:

- Type 2 shuga mellitus ngati monotherapy kuwonjezera pa zakudya ndi masewera olimbitsa thupi kuti mukwaniritse bwino glycemic control.

- lembani matenda ashuga a 2 monga njira yowonjezerapo mankhwala a metformin, a sulfonylurea otumphukira, thiazolidinedione, kuphatikiza kwa metformin ndi zotumphukira za sulfonylurea, kapena metformin ndi thiazoldinedione ngati glycemic yolamulira siyokwanira.

Zotsatira zoyipa za BAETA

Zotsatira zoyipa zomwe zimachitika nthawi zambiri kuposa zomwe zimachitika kamodzi zimalembedwa malinga ndi gradation yotsatirayi: nthawi zambiri (%10%), nthawi zambiri (%1%, koma zochita zamderalo: kawirikawiri - kuyabwa pamalo opangira jakisoni, kawirikawiri - zotupa, redness mu tsamba la jakisoni.

Kuchokera mmimba: kawirikawiri - nseru, kusanza, kutsegula m'mimba, kukomoka, kusowa chilakolako cha chakudya.

Kuchokera kumbali ya chapakati mantha dongosolo: nthawi zambiri - chizungulire.

Mukamagwiritsa ntchito Bayeta ® ngati monotherapy, kuchuluka kwa hypoglycemia kunali 5% poyerekeza ndi 1% placebo.

Magawo ambiri a hypoglycemia mwamphamvu anali ofatsa kapena odziletsa.

Zotsatira zoyipa zomwe zimachitika nthawi zambiri kuposa momwe zimakhalira padera zimalembedwa molingana ndi izi: pang'onopang'ono (≥10%), nthawi zambiri (≥1%, koma kuchokera kumimba yothandizira kugaya chakudya: Nthawi zambiri - nseru, kusanza, kutsegula m'mimba, kawirikawiri - kuchepa kulakalaka, dyspepsia, gastroesophageal Reflux, pafupipafupi - m'mimba kupweteka, kutulutsa, kugona, kudzimbidwa, kulawa chisokonezo, kugonja, kawirikawiri - kupweteka kwapweteka kwapafupipafupi. zosagwira.

Kuchokera kumbali ya dongosolo lamkati lamanjenje: Nthawi zambiri - chizungulire, kupweteka mutu, kawirikawiri - kugona.

Kuchokera ku endocrine system: nthawi zambiri - hypoglycemia (kuphatikiza ndi zotumphukira za sulfonylurea). Chifukwa kuchuluka kwa hypoglycemia kumawonjezeka ndi mgwirizano wa mankhwala a Bayeta ® okhala ndi zotumphukira za sulfonylurea, ndikofunikira kuti athe kuchepetsa kuchuluka kwa zotuluka za sulfonylurea ndi chiopsezo chowonjezeka cha hypoglycemia. Magawo ambiri a hypoglycemia mwamphamvu anali ofatsa kapena olimbitsa, ndipo amayimitsidwa ndi kudya kwa pakamwa.

Kuchokera kumbali ya kagayidwe: kawirikawiri - hyperhidrosis, kawirikawiri - kusowa kwamadzi (kumalumikizidwa ndi nseru, kusanza ndi / kapena kutsekula m'mimba).

Kuchokera kwamikodzo dongosolo: kawirikawiri - kusokonezeka kwa impso, kuphatikiza pachimake aimpso kulephera, kuchulukitsa kwa njira ya matenda aimpso kulephera, kuchuluka kwa seramu creatinine.

Thupi lawo siligwirizana: kawirikawiri - angioedema, osowa - anaphylactic reaction.

Zomwe zimachitika mdelalo: nthawi zambiri - kuyabwa pamalowo jakisoni, kawirikawiri - mwachangu, kufupika pamalo jakisoni.

Zina: nthawi zambiri - kunjenjemera, kufooka.

Milandu ingapo ya nthawi yowonjezereka yazakudya idanenedwa ndi kugwiritsidwa ntchito nthawi imodzi kwa warfarin ndi exenatide, komwe sikumachitika limodzi ndi magazi.

Mwambiri, zotsatilapo zake zinali zochepa kapena zolimbitsa kwambiri ndipo sizinachititse kuchoka pakulandila chithandizo.

Mauthenga ongodzipereka (otsatsa pambuyo)

Thupi lawo siligwirizana: kawirikawiri - anaphylactic anachita.

Mavuto azakudya ndi kagayidwe: kawirikawiri - kuchepa madzi m'thupi, kawirikawiri komwe kumalumikizidwa ndi nseru, kusanza komanso / kapena kutsekula m'mimba.

Kuchokera ku dongosolo lamanjenje: dysgeusia, kugona.

Kuchokera mmimba dongosolo: belching, kudzimbidwa, flatulence, kawirikawiri - pachimake kapamba.

Kuchokera kwamikodzo dongosolo: kusintha kwa impso, incl. pachimake aimpso kulephera, kuchulukitsa kwa aimpso kulephera, mkhutu aimpso ntchito, kuchuluka seramu creatinine ndende.

Dermatological zimachitika: zotupa za maculopapular, kuyabwa kwa khungu, urticaria, angioedema, alopecia.

Maphunziro a Laborator: kuwonjezeka kwa INR (akaphatikizidwa ndi warfarin), muzochitika zina zokhudzana ndi kukula kwa magazi.

Ngati mankhwala osokoneza bongo mlingo 10 nthawi pazovomerezeka mlingo: Zizindikiro zotsatirazi anati: kwambiri nseru ndi kusanza, komanso kukula kwa hypoglycemia.

Chithandizo: symptomatic mankhwala ikuchitika, kuphatikiza matenda a glucose makamaka hypoglycemia.

Bayeta ® iyenera kugwiritsidwa ntchito mosamala kwa odwala omwe akukonzekera kukamwa omwe amafunika kutuluka mofulumira m'mimba, monga Baeta ® imachedwetsa kuyamwa. Odwala ayenera kulangizidwa kumwa mankhwala pakamwa, momwe zimatengera mphamvu zawo (mwachitsanzo, mankhwala opha maantibayotiki), osachepera ola limodzi makonzedwe a exenatide. Ngati mankhwalawa amayenera kumwa ndi chakudya, ndiye kuti ayenera kumwedwa nthawi yomwe chakudya sichikuperekedwa.

Ndi makonzedwe a munthawi yomweyo a digoxin (0,25 mg 1 nthawi / tsiku) pokonzekera Baeta ®, max a C a digoxin amatsika ndi 17%, ndipo T max imawonjezeka ndi maola 2,5. Komabe, AUC yomwe ili mdziko lofanana sizisintha.

Ndi kukhazikitsidwa kwa Bayeta ®, AUC ndi C max ya lovastatin idatsika pafupifupi 40% ndi 28%, motero, ndipo T max idakwera pafupifupi maola 4. Kugwirizana kwa Bayeta ® yokhala ndi HMG-CoA reductase inhibitors sikunayendetsedwe ndi kusintha kwa kapangidwe ka magazi lipid (HDL) -cholesterol, LDL cholesterol, cholesterol yathunthu ndi TG).

Odwala omwe ali ndi matenda ochepa kapena ochepa ochita kuchepa kwa magazi, akhazikika pomwe akutenga lisinopril (5-20 mg / tsiku), Bayeta ® sinasinthe AUC ndi C max ya lisinopril pamlingo wofanana. T max of lisinopril pa equilibrium amawonjezeka ndi maola 2. Panalibe kusintha kulikonse pakati pamagazi a systolic ndi diastolic.

Zadziwika kuti pokhazikitsa warfarin mphindi 30 pambuyo pokonzekera Baeta ® T max amakula pafupifupi maola 2. Kusintha kwakukuru mu C max ndi AUC sikunachitike.

Kugwiritsa ntchito Bayeta ® kuphatikiza insulin, zochokera ku D-phenylalanine, meglitinide kapena alpha-glucosidase inhibitors sizinaphunzire.

Musamwe mankhwala mukatha kudya. Ndiwosavomerezeka mu / mu kapena / m kayendetsedwe ka mankhwalawa.

Bayeta ® sayenera kugwiritsidwa ntchito ngati tinthu tating'onoting'ono tapezeka mu yankho kapena ngati njirayo ili ndi mitambo kapena ili ndi utoto.

Chifukwa cha kufooka kwa mankhwala omwe ali ndi mapuloteni ndi ma peptides, kupanga ma antibodies of exenatide kumatha kuchitika panthawi ya mankhwala ndi Bayeta ®. Mwa odwala ambiri omwe kupanga mankhwala oterewa amadziwika, mankhwala awo am'mimba atachepa pomwe chithandizo chanapitirira ndikukhalabe otsika kwa masabata a 82. Kukhalapo kwa ma antibodies sikumakhudza ma frequency ndi mitundu ya zotsatirapo zoyipa.

Odwala ayenera kudziwitsidwa kuti chithandizo ndi Bayeta ® chitha kubweretsa kuchepa kwa chilimbikitso ndi / kapena kulemera kwa thupi, komanso kuti chifukwa cha izi palibe chifukwa chosinthira njira.

M'maphunziro oyesa mbewa ndi makoswe, palibe zotsatira zowononga thupi za exenatide. Mlingo womwe umagwiritsidwa ntchito mu makoswe omwe anali kuchuluka kwa kuchuluka kwa mankhwalawa 128 mwa anthu, kuchuluka kwa ma cell a C-cell adenomas kunadziwika popanda zisonyezo zilizonse, zomwe zimagwirizanitsidwa ndi kuchuluka kwa chiyembekezo cha nyama zoyesera zomwe zimalandira exenatide.

Nthawi zambiri vuto laimpso limanenedwa, kuphatikizapo kuwonjezeka kwa seramu creatinine, kukula kwa kulephera kwa impso, kukulitsa njira yolephera komanso yovuta yaimpso, ndipo nthawi zina hemodialysis imafunikira. Zina mwazinthu izi zimawonedwa mwa odwala omwe amalandila mankhwala amodzi kapena zingapo zamankhwala amkati zomwe zimakhudza kugwira ntchito kwa impso / madzi ndi / kapena zina zotsutsana ndi zochitika zina zomwe zimapangitsa kuti magazi asungunuke, monga nseru, kusanza ndi / kapena kutsegula m'mimba. Mankhwala olowa nawo anaphatikiza ACE inhibitors, NSAIDs, komanso okodzetsa. Mukamapereka mankhwala othandizira ndikuchotsa mankhwalawo, mwina chifukwa cha kusintha kwamatenda, minyewa yaimpso imabwezeretseka. Mukamachita kafukufuku wamakedzana komanso zamankhwala a exenatide, umboni wa nephrotoxicity mwachindunji sunapezeka.

Zovuta za pancreatitis pachimake zimanenedwa pamene mukutenga Bayeta ®. Odwala ayenera kudziwitsidwa za zomwe zimachitika ndi chifuwa chachikulu cha kapamba: kulimba kwam'mimba kwambiri. Mukamapereka mankhwala othandizira, kuthetsa pancreatitis ya pachimake kunawonedwa.

Odwala asanayambe chithandizo ndi Bayeta ® ayenera kudziphunzira ndi "Maupangiri ogwiritsa ntchito cholembera" omwe amaphatikizidwa ndi mankhwalawa.

Mndandanda B. Mankhwalawa amayenera kusungidwa pa kutentha kwa 2 ° mpaka 8 ° C. Moyo wa alumali ndi zaka 2.

Mankhwala ogwiritsidwa ntchito mu cholembera ayenera kusungidwa pa kutentha osaposa 25 ° C osapitirira masiku 30.

Mankhwala ayenera kusungidwa ndi ana, kutetezedwa pakuwala, osamasuka.