Pharmacokinetic and pharmacodynamic investigation of efavirenz in the semen and blood of human immunodeficiency virus type 1-infected men
Pharmacokinetic and pharmacodynamic investigation of efavirenz in the semen and blood of human immunodeficiency virus type 1-infected men
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DOI：
10.1086/344311
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发表时间：
2002-11-01
影响因子：
6.4
通讯作者：
Kashuba, ADM
中科院分区：
文献类型：
--
作者：
Reddy, YS;Gotzkowsky, SK;Kashuba, ADM
在精浆（SP）治疗浓度抗逆转录病毒药物可能减少病毒负担和影响人类免疫缺陷病毒（HIV） 1型的性传播。本研究比较了依非韦伦（EFV）在SP和血浆（BP）中的药代动力学、药效学和剂量反应。在40天的时间内，共从9名EFV初始男性（即第一次接受EFV的男性）和12名EFV经验男性（即已经接受EFV作为抗逆转录病毒治疗方案的一部分）中获得了431份BP样本和157份SP样本。总体而言，SP中位EFV暴露量为BP的3.4%（范围2.0%-5.0%）。然而，SP中所有EFV浓度都大于或等于HIV-1野生型IC90 （IC90WT）的40倍。在给药期间，没有单一的SP: BP efv浓度比显著预测SP暴露的绝对测量。到第40天，9名efv初发男性中有8名（89%）检测不到SP中的HIV-1 RNA， 12名efv经验男性中有10名（83%）检测不到SP中的HIV-1 RNA。在SP中，EFV在整个给药期间达到高于HIV-1 IC90WT的浓度。含efv方案有效抑制SP中HIV-1 RNA。
Therapeutic concentrations of antiretroviral agents in seminal plasma (SP) may reduce virus burden and influence sexual transmission of human immunodeficiency virus (HIV) type 1. This study compared the pharmacokinetic, pharmacodynamic, and dose responses of efavirenz (EFV) in SP versus those in blood plasma (BP). A total of 431 BP samples and 157 SP samples were obtained over a period of 40 days, from 9 EFV-naive men (i.e., men about to receive EFV for the first time) and from 12 EFV-experienced men (i.e., men already receiving EFV as part of an antiretroviral regimen). Overall, median EFV exposure in SP was 3.4% (range, 2.0%-5.0%) of that in BP. However, all EFV concentrations in SP were greater than or equal to40-fold higher than the wild-type IC90 (IC90WT) for HIV-1. During the dosing interval, no single SP: BP EFV-concentration ratio was significantly predictive of the absolute measure of exposure in SP. By day 40, HIV-1 RNA in SP was undetectable in 8 (89%) of 9 EFV-naive men and remained undetectable in 10 (83%) of 12 EFV-experienced men. In SP, EFV reaches concentrations above the HIV-1 IC90WT throughout the dosing interval. EFV-containing regimens effectively suppress HIV-1 RNA in SP.