Cobicistat versus ritonavir boosting and differences in the drug-drug interaction profiles with co-medications
Cobicistat versus ritonavir boosting and differences in the drug-drug interaction profiles with co-medications
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DOI：
10.1093/jac/dkw032
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发表时间：
2016-07-01
影响因子：
5.2
通讯作者：
Back, David
中科院分区：
文献类型：
--
作者：
Marzolini, Catia;Gibbons, Sara;Back, David
几乎所有HIV pi和整合酶抑制剂elvitegravir都需要药代动力学增强剂，以达到所需剂量和频率的治疗血浆浓度。十多年来，利托那韦一直是唯一可用的药代动力学增强剂，而共存司他最近成为一种替代的增强剂。Cobicistat和ritonavir是细胞色素P450 (CYP) 3A4的同样强的抑制剂，因此被证明是elvitegravir和PIs阿扎那韦和darunavir的等效药代动力学增强剂。由于cobicistat是一种比利托那韦更具选择性的CYP抑制剂，并且缺乏酶诱导特性，因此预计它们与一些联合药物的相互作用情况会有所不同。利托那韦改变暴露而共存司他不改变暴露的药物是主要由CYP1A2、CYP2B6、CYP2C8、CYP2C9和CYP2C19代谢的药物或主要发生糖醛酸化作用的药物。因此，在切换药代动力学增强剂时，应系统地审查联合用药，以预测潜在的剂量调整。
Nearly all HIV PIs and the integrase inhibitor elvitegravir require a pharmacokinetic enhancer in order to achieve therapeutic plasma concentrations at the desired dose and frequency. Whereas ritonavir has been the only available pharmacokinetic enhancer for more than a decade, cobicistat has recently emerged as an alternative boosting agent. Cobicistat and ritonavir are equally strong inhibitors of cytochrome P450 (CYP) 3A4 and consequently were shown to be equivalent pharmacokinetic enhancers for elvitegravir and for the PIs atazanavir and darunavir. Since cobicistat is a more selective CYP inhibitor than ritonavir and is devoid of enzyme-inducing properties, differences are expected in their interaction profiles with some co-medications. Drugs whose exposure might be altered by ritonavir but unaltered by cobicistat are drugs primarily metabolized by CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 or drugs undergoing mainly glucuronidation. Thus, co-medications should be systematically reviewed when switching the pharmacokinetic enhancer to anticipate potential dosage adjustments.