细胞色素p450的作用同功酶3和2 d6 mirabegron,体内新陈代谢的beta3-adrenoceptor受体激动剂。
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李J, Moy年代,梅耶尔J, Krauwinkel W, Sawamoto T, Kerbusch V,科瓦尔斯基D,罗伊M,马里昂,Takusagawa年代,van Gelderen M, Keirns J
细胞色素p450的作用同功酶3和2 d6 mirabegron,体内新陈代谢的beta3-adrenoceptor受体激动剂。
中国药物Investig。2013年6月,33 (6):429 - 40。doi: 10.1007 / s40261 - 013 - 0084 - y。
- PubMed ID
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23625188 (在PubMed]
- 文摘
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背景:Mirabegron beta3-adrenoceptor受体激动剂治疗膀胱过动症。没有信息发布或提交的参与细胞色素P450 (CYP)同功酶3和2 d6 mirabegron在人类的新陈代谢;beplayapp体外数据显示,氧化代谢主要是由CYP3A CYP2D6次要角色。目的:确定在多大程度上CYP3A CYP2D6和同功酶参与mirabegron新陈代谢。方法:两个非盲、随机、一个序列交叉药物之间的相互作用在健康受试者的研究进行了评估的影响酮康唑和利福平的药物动力学mirabegron和两个与这些相应平行的组织在健康受试者的研究被证实或预测CYP2D6表型。结果:合并施打多个400毫克/天的剂量与单个100毫克mirabegron口服酮康唑控制吸收系统(亚奥理事会)剂量增加mirabegron最大浓度(C (max))和曲线下的面积外推到正无穷(AUCinfinity)到145%(90%可信区间[CI] 123 - 172)和181% (90% CI 163 - 201),分别为。合并施打多个剂量600毫克/天利福平与单个100毫克mirabegron亚奥理事会剂量减少mirabegron C马克斯和AUCinfinity 65%(90%可信区间50 - 86 %)和56%(90%可信区间49 - 65 %),分别,不影响终端消除半衰期(t ((1/2)))。mirabegron的尿排泄是提高酮康唑和减少了利福平,反映了AUC变化,而肾清除率没有影响。酮康唑降低mirabegron t(1/2)从50.9到37.6 h表明体积分布以及初步的效果降低。利福平并不影响mirabegron t(1/2),这表明它影响首先通过肠壁和肝脏。 Rifampicin greatly increased the ratio to parent drug of the presumed CYP-mediated mirabegron metabolites M8 and M15 by 777 and 646 %. Steady-state mirabegron pharmacokinetic parameters (50 and 100 mg mirabegron OCAS) were similar in 13 CYP2D6 poor, 40 intermediate, and 99 extensive metabolizers, whereas C max and AUC under the dosing interval tau of 24 h (AUCtau) were 30-47 % lower in 10 ultrarapid metabolizers. After administration of 160 mg mirabegron immediate release, C(max) was 14 % and AUCinfinity 19 % higher in eight poor metabolizers than in eight extensive metabolizers (phenotyped) with similar t (1/2). All treatments were well tolerated. CONCLUSIONS: Mirabegron is metabolized by CYP3A and to a minor extent by CYP2D6 in humans. Mirabegron is not considered a sensitive substrate of CYP3A in vivo, as ketoconazole increased mirabegron exposure by less than 2-fold. The effect of CYP2D6 phenotype on mirabegron exposure is small and likely of limited clinical importance.
beplay体育安全吗DrugBank数据引用了这篇文章
- 药物酶
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药物 酶 类 生物 药理作用 行动 Mirabegron 细胞色素P450 2 d6 蛋白质 人类 没有底物抑制剂细节 Mirabegron 细胞色素P450 3 a4 蛋白质 人类 没有底物细节 - 药物的相互作用Learn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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药物 交互 整合药物之间
在您的软件的交互Mirabegron 酮康唑 的血清浓度Mirabegron时可以增加与酮康唑相结合。
