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 Flexner, Marta Boffito

Research output: Contribution to journalArticlepeer-review


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)
Article numberdkz068
Pages (from-to)1670-1678
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Issue number6
StatePublished - Jun 1 2019

ASJC Scopus subject areas

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


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