Unexpectedly low drug exposures among Ugandan patients with TB and HIV receiving high-dose rifampicin

Allan Kengo, Kamunkhwala Gausi, Ruth Nabisere, Joseph Musaazi, Allan Buzibye, Denis Omali, Rob Aarnoutse, Mohammed Lamorde, Kelly E. Dooley, Derek James Sloan, Christine Sekaggya-Wiltshire, Paolo Denti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

We characterized the pharmacokinetics of standard- and high-dose rifampicin in Ugandan adults with tuberculosis and HIV taking dolutegravir- or efavirenz-based antiretroviral therapy. A liver model with saturable hepatic extraction adequately described the data, and the increase in exposure between high and standard doses was 4.7-fold. This was lower than what previous reports of dose-exposure nonlinearity would predict and was ascribed to 38% lower bioavailability of the rifampicin-only top-up formulation compared to the fixed-dose combination.
Original languageEnglish
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume67
Issue number11
Early online date18 Oct 2023
DOIs
Publication statusPublished - 15 Nov 2023

Keywords

  • Rifampicin
  • High-dose
  • Pharmacokinetics
  • Bioavailability
  • Top-up capsule

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