西洛地唑抑制CYP3A的代谢影响。

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苏瑞,福布斯WP,布拉姆SL

西洛地唑抑制CYP3A的代谢影响。

Pharmacokinet。1999; 37增刊2:61-8。

PubMed ID

10702888 (在PubMed

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目的:体外研究结果表明,西洛地唑生物新陈代谢的细胞色素P450 (CYP)亚型1 a2, 2 d6, 3和2 c19。本研究调查了西洛地唑抑制CYP3A的代谢作用。设计:这项研究是作为一个只有,进行非盲、nonrandomised -周期交叉药代动力学试验。西洛地唑的单剂量100毫克口服药物在第1和15天。红霉素(每天150毫克口服3次)在8到20天。14 c-erythromycin(3微米Ci)是管理静脉注射在第1和15天1小时前西洛地唑政府确定基线和红霉素治疗CYP3A活性的抑制作用。研究对象:16健康不吸烟的男性志愿者。主要结果测量:串行集中尿液和血液样本收集西洛地唑前后政府量化西洛地唑及其代谢物。串行呼气样本收集静脉注射后14 c-erythromycin放射性被闪烁计数量化和管理。药物动力学测定红霉素前后相比noncompartmental方法和管理。 Tolerability assessments included adverse events, laboratory tests, vital signs and electrocardiographs. RESULTS: Following erythromycin coadministration, cilostazol maximum plasma concentration (Cmax), area under the plasma concentration-time curve at time t (AUCt), and area under the curve from zero to infinity (AUC infinity) increased significantly by 47, 87, and 73%, respectively, and an approximately 50% reduction in unbound clearance was observed for the major circulating metabolite of cilostazol, OPC-13015. Cmax decreased significantly (p < 0.001) by 24%, while AUCt increased by 8%; this increase was not significant. For the second major metabolite, OPC-13213, the Cmax and AUCt increased by 29 and 141%, respectively (p < 0.001). CONCLUSIONS: In vivo results are in agreement with previous in vitro human microsome studies, indicating that cilostazol is metabolised to OPC-13015 via CYP3A. In addition, OPC-13213 concentrations increased after inhibition of CYP3A because of inhibition of sequential metabolism of OPC-13213 via CYP3A. A starting dose for cilostazol of 50 mg twice daily should be considered during coadministration of inhibitors of CYP3A.

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药物酶

药物	酶	类	生物	药理作用	行动
西洛地唑	细胞色素P450 1 a2	蛋白质	人类	未知的	底物	细节
西洛地唑	细胞色素P450 2 c19	蛋白质	人类	未知的	底物	细节
西洛地唑	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节
西洛地唑	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节
西洛地唑	细胞色素P450 3 a5	蛋白质	人类	未知的	底物	细节
西洛地唑	细胞色素P450 3 a7	蛋白质	人类	未知的	底物	细节