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

Research output: Contribution to journalArticle

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 (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.

Original languageEnglish (US)
JournalClinical Pharmacology and Therapeutics
DOIs
StateAccepted/In press - Jan 1 2019

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Tenofovir
Probenecid
Pharmacokinetics
HIV
Cross-Over Studies
Emtricitabine
Blood Cells
Healthy Volunteers

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Inhibitory Effects of Probenecid on Pharmacokinetics of Tenofovir Disoproxil Fumarate and Emtricitabine for On-Demand HIV Preexposure Prophylaxis. / Liu, Stephanie N.; Gufford, Brandon T.; Lu, Jessica Bo Li; Bushman, Lane R.; Anderson, Peter L.; Bergstrom, Richard F.; Desta, Zeruesenay; Gupta, Samir K.

In: Clinical Pharmacology and Therapeutics, 01.01.2019.

Research output: Contribution to journalArticle

Liu, Stephanie N. ; Gufford, Brandon T. ; Lu, Jessica Bo Li ; Bushman, Lane R. ; Anderson, Peter L. ; Bergstrom, Richard F. ; Desta, Zeruesenay ; Gupta, Samir K. / Inhibitory Effects of Probenecid on Pharmacokinetics of Tenofovir Disoproxil Fumarate and Emtricitabine for On-Demand HIV Preexposure Prophylaxis. In: Clinical Pharmacology and Therapeutics. 2019.
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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 (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.",
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