Rifampicin effect on intracellular and plasma pharmacokinetics of tenofovir alafenamide

Maddalena Cerrone, Omamah Alfarisi, Megan Neary, Mark A Marzinke, Teresa L. Parsons, Andrew Owen, Gary Maartens, Anton Pozniak, Charles Williams Flexner, Marta Boffito

Research output: Contribution to journalArticle


OBJECTIVES: Tenofovir alafenamide produces lower plasma tenofovir and higher intracellular tenofovir diphosphate (DP) concentrations than tenofovir disoproxil fumarate but it is likely a victim of interactions with rifampicin. We aimed to investigate the pharmacokinetics of tenofovir alafenamide/emtricitabine with rifampicin. PATIENTS AND METHODS: Healthy volunteers received tenofovir alafenamide/emtricitabine at 25/200 mg once daily, followed by tenofovir alafenamide/emtricitabine + rifampicin daily followed by tenofovir disoproxil fumarate. Plasma tenofovir alafenamide, tenofovir, emtricitabine and intracellular tenofovir-DP and emtricitabine triphosphate pharmacokinetics and genetic polymorphisms were assessed. RESULTS: Tenofovir alafenamide exposure decreased when tenofovir alafenamide/emtricitabine + rifampicin was used compared with tenofovir alafenamide/emtricitabine [geometric mean ratio (GMR) (90% CI): 0.45 (0.33-0.60)]. Plasma tenofovir and intracellular tenofovir-DP concentrations decreased with rifampicin [GMR (90% CI): 0.46 (0.40-0.52) and 0.64 (0.54-0.75), respectively]. GMR (90% CI) of intracellular tenofovir-DP AUC0-24 for tenofovir alafenamide/emtricitabine + rifampicin versus tenofovir disoproxil fumarate was 4.21 (2.98-5.95). Rifampicin did not affect emtricitabine pharmacokinetics. CYP3A4*22 rs35599367 was associated with higher plasma tenofovir alafenamide AUC0-24 at day 56. CONCLUSIONS: Following tenofovir alafenamide/emtricitabine administration with rifampicin, intracellular tenofovir-DP concentrations were still 4.21-fold higher than those achieved by tenofovir disoproxil fumarate, supporting further study during HIV/TB co-infection.

Original languageEnglish (US)
Pages (from-to)1670-1678
Number of pages9
JournalThe Journal of antimicrobial chemotherapy
Issue number6
StatePublished - Jun 1 2019


ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Cerrone, M., Alfarisi, O., Neary, M., Marzinke, M. A., Parsons, T. L., Owen, A., Maartens, G., Pozniak, A., Flexner, C. W., & Boffito, M. (2019). Rifampicin effect on intracellular and plasma pharmacokinetics of tenofovir alafenamide. The Journal of antimicrobial chemotherapy, 74(6), 1670-1678. https://doi.org/10.1093/jac/dkz068