英迪纳维
萨奎纳维尔
利托那韦
丁丙诺啡
美沙酮
药理学
蛋白酶抑制剂(药理学)
CYP3A4型
化学
蛋白酶
药物相互作用
医学
药品
细胞色素P450
酶
病毒学
生物化学
西达
类阿片
病毒
病毒载量
病毒性疾病
受体
抗逆转录病毒疗法
作者
Christelle Iribarne,François Berthou,Carlhant D,Yvonne Dréano,Daniel Picart,F. Lohezic,Christian Riche
摘要
Ritonavir, indinavir, and saquinavir, all human immunodeficiency virus-1 protease inhibitors with a potent antiviral effect during triple therapy, are extensively metabolized by liver cytochrome P450 3A4. As this P450 isoform is involved in the metabolism of about 50% of drugs, coadministration of protease inhibitors with other drugs may lead to serious effects due to enzyme inhibition. Among these drugs, methadone and buprenorphine, both metabolized by P450 3A4, are potential candidates to drug interactions. In this study, metabolic interactions between these protease inhibitors and methadone or buprenorphine were studied in vitro in a panel of 13 human liver microsomes. Ritonavir was the most potent competitive inhibitor with Ki about 50 and 20 nM for methadone and buprenorphine metabolisms, respectively. Indinavir and saquinavir also inhibited methadone N-demethylation (Ki about 3 and 15 microM, respectively) and buprenorphine N-dealkylation (Ki about 0.8 and 7 microM, respectively). The rank order of inhibition potency against metabolism of methadone and buprenorphine was ritonavir > indinavir > saquinavir. There is obvious potential for clinically significant drug interactions, particularly with ritonavir. In brief, caution should be advised if human immunodeficiency virus-1 protease inhibitors are coadministered with methadone and buprenorphine.
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