Pharmacology of HIV integrase inhibitors.
Pharmacology of HIV integrase inhibitors.
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DOI：
10.1097/coh.0b013e328356e91c
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发表时间：
2012-09
影响因子：
4.1
通讯作者：
Kashuba AD
中科院分区：
文献类型：
--
作者：
Adams JL;Greener BN;Kashuba AD
本文的目的是回顾三种HIV整合酶抑制剂的最新和相关药理学数据：雷替格拉韦（已上市），多替格拉韦和埃韦替格拉韦（均处于III期药物开发）。对2011年1月至2012年4月的数据进行评估。这些数据更好地表征了整合酶抑制剂的药代动力学，评估了给药方案，并研究了先前未描述的药物-药物相互作用。由于配方方面的挑战，雷替重力韦在患者之间和患者内部的药代动力学变异性很高。每日两次400mg剂量已被证明优于每日一次800mg剂量。2011年12月，FDA批准了一种药代动力学变化较小、生物利用度更高的雷替格拉韦儿科制剂。cobicistat增强的elvitegravir和第二代整合酶抑制剂dolutegravir具有较低的药代动力学变异性，并且每天给药一次。杜替格拉韦药物相互作用类似于雷替格拉韦，而增强的艾替格拉韦参与额外的CYP3A介导的相互作用。雷替格拉韦的有效抗逆转录病毒活性已导致广泛使用治疗naïve和有经验的患者。多替重力韦和共比司他增强型依替重力韦在药代动力学上有一些优势。特殊人群（妊娠、儿科）的药代动力学数据仍需优化剂量。
The purpose of this paper is to review recent and relevant pharmacology data for three HIV integrase inhibitors: raltegravir (marketed), dolutegravir and elvitegravir (both in Phase III drug development). Data from January 2011 to April 2012 were evaluated. These data better characterized integrase inhibitor pharmacokinetics, assessed dosing regimens and investigated previously undescribed drug-drug interactions. Due to formulation challenges, raltegravir inter- and intra-patient pharmacokinetic variability is high. Twice daily 400mg dosing has been shown to be clinically superior to 800mg once daily dosing. A pediatric formulation of raltegravir with less variable pharmacokinetics and greater bioavailability was FDA approved in December 2011. Cobicistat-boosted elvitegravir, and the second generation integrase inhibitor dolutegravir, have lower pharmacokinetic variability and are dosed once daily. Dolutegravir drug interactions are similar to raltegravir, while boosted elvitegravir participates in additional CYP3A mediated interactions. Raltegravir’s potent antiretroviral activity has resulted in widespread use in both treatment naïve and experienced patients. Dolutegravir and cobicistat-boosted elvitegravir have some pharmacokinetic advantages. Pharmacokinetic data in special populations (pregnancy, pediatrics) to optimize dosing are still required.