Inhibitory Effects of Probenecid on Pharmacokinetics of Tenofovir Disoproxil Fumarate and Emtricitabine for On-Demand HIV Preexposure Prophylaxis.

Stephanie N Liu, Brandon T Gufford, Jessica Bo Li Lu, Lane R Bushman, Peter L Anderson, Richard F Bergstrom, Zeruesenay Desta, Samir K Gupta

Clinical pharmacology and therapeutics 2020 May

filter terms:

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 (AUC0-∞,SD ) of tenofovir (TFV) and FTC by 61% and 68%, respectively. The TFV-diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells were higher (~30%) at 24 hours in T +PRO but then fell significantly lower (~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. © 2019 The Authors. Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.

Citation

Stephanie N Liu, Brandon T Gufford, Jessica Bo Li Lu, Lane R Bushman, Peter L Anderson, Richard F Bergstrom, Zeruesenay Desta, Samir K Gupta. Inhibitory Effects of Probenecid on Pharmacokinetics of Tenofovir Disoproxil Fumarate and Emtricitabine for On-Demand HIV Preexposure Prophylaxis. Clinical pharmacology and therapeutics. 2020 May;107(5):1200-1208