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

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.

SUBMITTER: Kengo A 

PROVIDER: S-EPMC10649026 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature