的First-in-Class Potassium-Competitive酸阻滞剂,Vonoprazan延胡索酸酯:药代动力学和药效学方面的考虑。

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Echizen H

的First-in-Class Potassium-Competitive酸阻滞剂,Vonoprazan延胡索酸酯:药代动力学和药效学方面的考虑。

55 Pharmacokinet。2016年4月;(4):409 - 18。doi: 10.1007 / s40262 - 015 - 0326 - 7。

PubMed ID

26369775 (在PubMed

]

文摘

Vonoprazan延胡索酸酯(Takecab)是一个first-in-class potassium-competitive酸阻滞剂,2015年2月以来在日本市场上。Vonoprazan口服药物在20毫克每天一次治疗胃十二指肠溃疡,20岁和10毫克每日一次,反流性食管炎的治疗和二级预防,分别在10毫克每天一次的二级预防低剂量的阿司匹林或非甾体抗炎药物引起的消化性溃疡,和20毫克每日两次结合克拉霉素、阿莫西林为根除幽门螺杆菌。它能抑制H (+), K(+)腺苷三磷酸酶活动一个可逆和potassium-competitive方式抑制能力的大约350倍的质子泵抑制剂,lansoprazole。Vonoprazan迅速被吸收,达到最大血浆浓度在1.5 - -2.0 h后口服。食物在肠道的吸收有一定的作用。口服生物利用度在人类仍然是未知的。血浆蛋白结合在健康受试者vonoprazan是80%。它广泛分布到组织平均表观分布容积1050 l .基地pKa 9.6和耐酸性能,vonoprazan高度集中在酸性胃壁细胞的微管和引起酸抑制效应超过24小时后20毫克的管理。均值明显终端药物的半衰期是大约7.7 h在健康成年人。Vonoprazan是代谢活性代谢产物主要由细胞色素P450 (CYP) 3 a4和CYP2B6在某种程度上,CYP2C19、CYP2D6、SULT2A1。 A mass balance study showed that 59 and 8% of the orally administered radioactivity was recovered in urine as metabolites and in an unchanged form, respectively, indicating extensive metabolism. Genetic polymorphism of CYP2C19 may influence drug exposure but only to a clinically insignificant extent (15-29%), according to the population pharmacokinetic study performed in Japanese patients. When vonoprazan was co-administered with clarithromycin, the mean AUC from time 0 to time of the next dose (dosing interval) of vonoprazan and clarithromycin were increased by 1.8 and 1.5 times, respectively, compared with the corresponding control values, indicating mutual metabolic inhibition. The mean area under the curve from time zero to infinity obtained from patients with severe liver and renal dysfunction were elevated by 2.6 and 2.4 times, respectively, compared with healthy subjects, with no significant changes in plasma protein binding. Vonoprazan increases intragastric pH above 4.0 as early as 4 h after an oral dose of 20 mg, and the extensive anti-secretory effect is maintained up to 24 h post-dose. During repeated dosing of 20 mg once daily, the 24-h intragastric pH >4 holding time ratios were 63 and 83 % on days 1 and 7, respectively. Because vonoprazan elicited a more extensive gastric acid suppression than the proton pump inhibitor, lansoprazole, it also gave rise to two to three times greater serum gastrin concentrations as compared with lansoprazole. In pre-approval clinical studies for the treatment of acid-related disorders, mild to moderate adverse drug reactions (mostly constipation or diarrhea) occurred at frequencies of 8-17%. Neither severe liver toxicity nor neuroendocrine tumor has been reported in patients receiving vonoprazan.

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药物

Vonoprazan

药物酶

药物	酶	类	生物	药理作用	行动
Vonoprazan	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节

药物载体

药物	航空公司	类	生物	药理作用	行动
Vonoprazan	Alpha-1-acid糖蛋白1	蛋白质	人类	未知的	粘结剂	细节
Vonoprazan	血清白蛋白	蛋白质	人类	未知的	粘结剂	细节

药物转运蛋白

药物	转运体	类	生物	药理作用	行动
Vonoprazan	22 - 1	蛋白质	人类	未知的	抑制剂	细节