Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Curr Opin HIV AIDS. 2012 Sep;7(5):390-400. doi: 10.1097/COH.0b013e328356e91c.
The purpose of this study 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-patient and intra-patient pharmacokinetic variability is high. Twice-daily 400 mg dosing has been shown to be clinically superior to 800 mg once-daily dosing. A pediatric formulation of raltegravir with less variable pharmacokinetics and greater bioavailability was US Food and Drug Administration (US 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, whereas 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.
本研究旨在综述三种 HIV 整合酶抑制剂（拉替拉韦[已上市]、多替拉韦和艾维雷格[均处于 III 期药物研发阶段]）的近期相关药理学数据。
评估了 2011 年 1 月至 2012 年 4 月的数据。这些数据更好地描述了整合酶抑制剂的药代动力学特征，评估了给药方案，并研究了以前未描述的药物相互作用。由于制剂方面的挑战，拉替拉韦的个体间和个体内药代动力学变异性较高。每日两次 400 毫克的给药方案已被证明优于每日一次 800 毫克的给药方案。拉替拉韦的一种儿科制剂具有较少的变异性和更高的生物利用度，已于 2011 年 12 月获得美国食品药品监督管理局（FDA）批准。考比司他增强型艾维雷格和第二代整合酶抑制剂多替拉韦的药代动力学变异性较低，每日给药一次。多替拉韦的药物相互作用与拉替拉韦相似，而考比司他增强型艾维雷格则参与了更多的 CYP3A 介导的相互作用。
拉替拉韦具有强大的抗逆转录病毒活性，已在治疗初治和经验丰富的患者中广泛使用。多替拉韦和考比司他增强型艾维雷格具有一些药代动力学优势。仍需要针对特殊人群（妊娠、儿科）优化剂量的药代动力学数据。
