Pharmacokinetics of emtricitabine/tenofovir disoproxil fumarate and tacrolimus at steady state when administered alone or in combination

Int J Clin Pharmacol Ther. 2008 Dec;46(12):627-36. doi: 10.5414/cpp46627.

Abstract

Objective: An open-label, randomized, 3-way crossover, drug-drug interaction study of the investigational anti-HBV combination agent, emtricitabine/tenofovir DF and the antirejection agent, tacrolimus was conducted in healthy volunteers to evaluate the potential for a pharmacokinetic interaction between these drugs.

Methods: Subjects received emtricitabine/tenofovir DF (200/300 mg q.d.) and tacrolimus (0.1 mg/kg/day) alone or in combination for 7 days, with a 2-week washout between successive treatments. Drug concentrations were measured by LC/MS/MS and steady state pharmacokinetic parameters were calculated for each drug using noncompartmental methods.

Results: The 90% confidence intervals (CIs) of the geometric least-squares mean ratio for AUCtau, Cmax and Ctau for each drug together vs. alone were within the predetermined no-effect boundaries of 80 - 125% (representing a maximum 20% effect), other than the upper limit of the 90% CI for tenofovir Cmax, which was just outside the 125% threshold.

Conclusions: It was concluded that there was no clinically relevant pharmacokinetic interaction between emtricitabine/tenofovir DF and tacrolimus when administered together.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / blood
  • Adenine / pharmacokinetics
  • Adult
  • Area Under Curve
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / blood
  • Deoxycytidine / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Emtricitabine
  • Female
  • Flatulence / chemically induced
  • Half-Life
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacokinetics
  • Male
  • Middle Aged
  • Nervous System Diseases / chemically induced
  • Organophosphonates / adverse effects
  • Organophosphonates / blood
  • Organophosphonates / pharmacokinetics*
  • Patient Dropouts / statistics & numerical data
  • Tacrolimus / adverse effects
  • Tacrolimus / blood
  • Tacrolimus / pharmacokinetics*
  • Tenofovir
  • Time Factors
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Organophosphonates
  • Deoxycytidine
  • Tenofovir
  • Emtricitabine
  • Adenine
  • Tacrolimus