Inhibitory Effects of Probenecid on Pharmacokinetics of Tenofovir Disoproxil Fumarate and Emtricitabine for On-Demand HIV Preexposure Prophylaxis
- 30 December 2019
- journal article
- research article
- Published by Wiley in Clinical Pharmacology & Therapeutics
- Vol. 107 (5), 1200-1208
- https://doi.org/10.1002/cpt.1714
Abstract
In a randomized, crossover pharmacokinetic study in healthy volunteers (N = 14), a single dose of 2 g probenecid (PRO)-boosted 600 mg tenofovir disoproxil fumarate (TDF)/400 mg emtricitabine (FTC) (test (T) +PRO) was compared with the current on-demand HIV preexposure prophylaxis from the IPERGAY study (a 600 mg TDF/400 mg FTC on day 1 and 300 mg TDF/200 mg FTC on days 2 and 3) (control, C IPERGAY). PRO increased mean single-dose area under the plasma concentration-time curve extrapolated to infinity (AUC(0-infinity,SD)) of tenofovir (TFV) and FTC by 61% and 68%, respectively. The TFV-diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells were higher (similar to 30%) at 24 hours in T +PRO but then fell significantly lower (similar to 40%) at 72 hours compared with C IPERGAY. The interaction between FTC and PRO was unexpected and novel. Further study is needed to determine if this PRO-boosted TDF/FTC regimen would be clinically effective.Keywords
Funding Information
- Indiana Clinical and Translational Sciences Institute
- National Institutes of Health (UL1TR002529)
- National Center for Advancing Translational Sciences
- National Institute of General Medical Sciences (T32 GM008425, R01s GM078501, GM121707)
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