Dumond Julie B, Yeh Rosa F, Patterson Kristine B, Corbett Amanda H, Jung Byung Hwa, Rezk Naser L, Bridges Arlene S, Stewart Paul W, Cohen Myron S, Kashuba Angela D M
School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina, USA.
AIDS. 2007 Sep 12;21(14):1899-907. doi: 10.1097/QAD.0b013e328270385a.
To describe first dose and steady state antiretroviral drug exposure in the female genital tract.
Non-blinded, single center, open-label pharmacokinetic study in HIV-infected women.
Twenty-seven women initiating combination antiretroviral therapy underwent comprehensive blood plasma and cervicovaginal fluid sampling for drug concentrations during the first dose of antiretroviral therapy and at steady-state. Drug concentrations were measured by validated HPLC/UV or HPLC-MS/MS methods. Pharmacokinetic parameters were estimated for 11 drugs by non-compartmental analysis. Descriptive statistics and 95% confidence intervals were generated using Intercooled STATA Release 8.0 (Stata Corporation, College Station, Texas, USA).
For all antiretroviral drugs, genital tract concentrations were detected rapidly after the first dose. Drugs were stratified according to the genital tract concentrations achieved relative to blood plasma. Median rank order of highest to lowest genital tract concentrations relative to blood plasma at steady state were: lamivudine (concentrations achieved were 411% greater than blood plasma), emtricitabine (395%), zidovudine (235%) tenofovir (75%), ritonavir (26%), didanosine (21%), atazanavir (18%), lopinavir (8%), abacavir (8%), stavudine (5%), and efavirenz (0.4%).
This is the first study to comprehensively evaluate antiretroviral drug exposure in the female genital tract. These findings support the use of lamivudine, zidovudine, tenofovir and emtricitabine as excellent pre-exposure/post-exposure prophylaxis (PrEP/PEP) candidates. Atazanavir and lopinavir might be useful agents for these applications due to favorable therapeutic indices, despite lower genital tract concentrations. Agents such as stavudine, abacavir, and efavirenz that achieve genital tract exposures less than 10% of blood plasma are less attractive PrEP/PEP candidates.
描述抗逆转录病毒药物在女性生殖道中的首剂暴露和稳态暴露情况。
针对感染HIV的女性进行的非盲、单中心、开放标签的药代动力学研究。
27名开始接受联合抗逆转录病毒治疗的女性在抗逆转录病毒治疗首剂给药期间及稳态时接受了全面的血浆和宫颈阴道液采样以检测药物浓度。药物浓度通过经验证的高效液相色谱/紫外检测法（HPLC/UV）或高效液相色谱-串联质谱法（HPLC-MS/MS）进行测定。通过非房室分析估算了11种药物的药代动力学参数。使用Intercooled STATA Release 8.0（美国德克萨斯州大学城的Stata公司）生成描述性统计数据和95%置信区间。
对于所有抗逆转录病毒药物，首剂给药后很快就能在生殖道中检测到药物浓度。根据相对于血浆所达到的生殖道浓度对药物进行分层。稳态时相对于血浆生殖道浓度从高到低的中位数排序为：拉米夫定（所达到的浓度比血浆高411%）、恩曲他滨（395%）、齐多夫定（235%）、替诺福韦（75%）、利托那韦（26%）、去羟肌苷（21%）、阿扎那韦（18%）、洛匹那韦（8%）、阿巴卡韦（8%）、司他夫定（5%）和依非韦伦（0.4%）。
这是第一项全面评估抗逆转录病毒药物在女性生殖道中暴露情况的研究。这些发现支持将拉米夫定、齐多夫定、替诺福韦和恩曲他滨用作暴露前/暴露后预防（PrEP/PEP）的理想候选药物。尽管生殖道浓度较低，但由于具有良好的治疗指数，阿扎那韦和洛匹那韦可能是用于这些应用的有用药物。像司他夫定、阿巴卡韦和依非韦伦这样在生殖道中的暴露量不到血浆10%的药物作为PrEP/PEP候选药物的吸引力较小。
