| Literature DB >> 31002391 |
Stephen A Greene1,2, Jingxian Chen1,3, Heather M A Prince4, Craig Sykes1, Amanda P Schauer1, Kimberly Blake1, Julie A E Nelson5, Cynthia L Gay4, Myron S Cohen4, Julie B Dumond1.
Abstract
Understanding antiretroviral disposition in the male genital tract, a distinct viral compartment, can provide insight for the eradication of HIV. Population pharmacokinetic modeling was conducted to investigate the disposition of tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and emtricitabine and their metabolites in blood and semen. Blood plasma and seminal plasma (SP) concentrations of tenofovir and emtricitabine were measured, as were tenofovir-diphosphate and emtricitabine-triphosphate concentrations in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells. Sequential compartmental modeling described drug disposition in blood and semen. Our modeling suggests slower elimination of apparent tenofovir-diphosphate PBMC and faster elimination of tenofovir SP after administration of TAF compared with TDF, likely reflecting flip-flop kinetics. Additionally, TAF metabolism to tenofovir appeared slower in semen compared with blood; however, SP elimination of TAF-derived tenofovir appeared faster than its blood plasma elimination. These findings provide valuable insight for further mechanistic study of cellular entry and drug metabolism in the male genital tract.Entities:
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Year: 2019 PMID： 31002391 PMCID： PMC7079728 DOI： 10.1002/cpt.1464
Source DB: PubMed Journal: Clin Pharmacol Ther ISSN： 0009-9236 Impact factor: 6.875