艾普拉唑和氯吡格雷在人体内的药代动力学相互作用

Pharmacokinetic interaction between ilaprazole and clopidogrel in humans

摘要

目的: 在健康受试者中评估稳态条件下艾普拉唑对氯吡格雷药代动力学的影响。方法: 本研究采用随机、开放、交叉、自身对照试验设计。入组40例健康受试者,随机分为A、B两组,每组20例,A组予氯吡格雷75 mg,每日1次,连续给药7 d;B组予氯吡格雷75 mg+艾普拉唑10 mg,每日1次,连续给药7 d。经10 d清洗期后,两组交叉给药方案继续试验。测定氯吡格雷、氯吡格雷活性代谢物及氯吡格雷羧酸的血药浓度,用于药代动力学分析。结果: 氯吡格雷活性代谢物的系统暴露量在总人群及CYP2C19强代谢者中,几何均值比的90%CI均在0.80~1.25等效区间内。结论: 健康受试者中,艾普拉唑与氯吡格雷未见具有临床显著意义的药代动力学相互作用;在CYP2C19强代谢受试者中,亦无明显临床相关性。

Abstract

Objective: To evaluate the effect of steady-state ilaprazole on the pharmacokinetics of clopidogrel in healthy subjects. Methods: A randomized, open-label, crossover, self-controlled trial was conducted. A total of 40 healthy subjects were randomly assigned to two groups (Group A and Group B, n = 20 each). Group A received clopidogrel 75 mg once daily for 7 consecutive days; Group B received clopidogrel 75 mg plus ilaprazole 10 mg once daily for 7 days. After a 10-day washout period, the two groups crossed over to the alternative regimen. Plasma concentrations of clopidogrel, its active metabolite, and clopidogrel carboxylic acid were determined for pharmacokinetic analysis. Results: The 90%CI of the geometric mean ratios for systemic exposure of clopidogrel active metabolite in the all subjects and CYP2C19 extensive metabolizers were within the range of 0.80 to 1.25. Conclusion: No clinically significant pharmacokinetic interaction was observed between ilaprazole and clopidogrel in healthy subjects, nor was there obvious clinical relevance in CYP2C19 extensive metabolizers.

关键词

氯吡格雷 / 艾普拉唑 / 药物相互作用 / 药代动力学 / 质子泵抑制剂 / CYP2C19 / 活性代谢物

Key words

clopidogrel / ilaprazole / drug-drug interaction / pharmacokinetics / proton pump inhibitor / CYP2C19 / active metabolite

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基金资助

国家十三五重大新药创制专项(2018ZX09734-007)