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Rifampicin effect on intracellular and plasma pharmacokinetics of tenofovir alafenamide

Maddalena Cerrone1, Omamah Alfarisi2, Megan Neary3

  • 1St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.

The Journal of Antimicrobial Chemotherapy
|March 1, 2019
PubMed
Abstract

Insights

Rifampicin significantly reduces tenofovir alafenamide levels but intracellular tenofovir diphosphate remains higher than with tenofovir disoproxil fumarate. Further research is needed for HIV/TB co-infection treatment.

Area of Science:

  • Pharmacology
  • Drug Interactions
  • HIV/TB Co-infection

Background:

  • Tenofovir alafenamide (TAF) offers improved intracellular tenofovir diphosphate (DP) concentrations compared to tenofovir disoproxil fumarate (TDF).
  • Rifampicin, a key treatment for tuberculosis (TB), is known to interact with various medications.
  • Investigating TAF pharmacokinetics with rifampicin is crucial for managing patients with Human Immunodeficiency Virus (HIV) and TB co-infection.

Purpose of the Study:

  • To evaluate the pharmacokinetic interactions between tenofovir alafenamide/emtricitabine (TAF/FTC) and rifampicin.
  • To compare intracellular tenofovir diphosphate (DP) concentrations achieved by TAF/FTC with and without rifampicin, and against TDF.

Main Methods:

  • Healthy volunteers received TAF/FTC, followed by TAF/FTC plus rifampicin, and then TDF.
  • Plasma concentrations of TAF, tenofovir, and emtricitabine were measured.
  • Intracellular tenofovir-DP and emtricitabine triphosphate levels were assessed, along with genetic polymorphisms.

Main Results:

  • Concomitant use of rifampicin significantly decreased TAF exposure (GMR 0.45) and plasma tenofovir levels (GMR 0.46).
  • Intracellular tenofovir-DP concentrations were reduced by rifampicin (GMR 0.64) but remained 4.21-fold higher than TDF.
  • Rifampicin did not impact emtricitabine pharmacokinetics; CYP3A4*22 polymorphism influenced TAF AUC.

Conclusions:

  • Despite rifampicin-induced reductions, TAF/FTC maintains significantly higher intracellular tenofovir-DP levels compared to TDF.
  • These findings support the potential utility of TAF/FTC in HIV/TB co-infected individuals, warranting further investigation.

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