Cottrell Mackenzie L, Srinivas Nithya, Kashuba Angela D M
University of North Carolina, UNC Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics , 1094 Genetic Medicine Building, CB# 7361, 120 Mason Farm Road, Chapel Hill, NC 27599 , USA +1 919 966 9998 ; +1 919 962 0644 ;
Expert Opin Drug Metab Toxicol. 2015 Jun;11(6):893-905. doi: 10.1517/17425255.2015.1027682. Epub 2015 Mar 22.
In the absence of an HIV vaccine or cure, antiretroviral (ARV)-based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site of HIV exposure, which is most commonly the mucosal tissue of the lower gastrointestinal tract and the female genital tract.
This article collates all known data regarding drug exposure in these vulnerable mucosal tissues and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing ARV pharmacokinetics (PK) in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport and endogenous hormones are also reviewed.
ARVs exhibit highly variable PK in mucosal tissues. In general, ARV exposure is higher in the lower gastrointestinal tract compared with the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing ARV-based prevention strategies.
在缺乏HIV疫苗或治愈方法的情况下，正在研究基于抗逆转录病毒（ARV）的预防策略以降低HIV发病率。这些预防策略依赖于在HIV暴露部位达到有效的药物浓度，该部位最常见的是下消化道和女性生殖道的粘膜组织。
本文整理了有关这些脆弱粘膜组织中药物暴露的所有已知数据，并综述了ARV药物分布的重要机制。详细回顾了2014年12月之前在MEDLINE®中可获取或在科学会议上发表的描述女性生殖道和下消化道粘膜组织中ARV药代动力学（PK）的研究论文和摘要。还综述了对ARV粘膜组织分布的重要影响，包括蛋白质结合、活性药物转运和内源性激素。
ARV在粘膜组织中的PK表现出高度变异性。一般而言，与女性生殖道相比，下消化道中的ARV暴露更高，但保护效力所需的浓度在很大程度上尚不清楚。在设计和优化基于ARV的预防策略时，预期的HIV暴露部位是一个重要的考虑因素。
