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

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...

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Bibliographic Details
Published inAntimicrobial agents and chemotherapy Vol. 67; no. 11; p. e0043123
Main Authors Kengo, Allan, Gausi, Kamunkhwala, Nabisere, Ruth, Musaazi, Joseph, Buzibye, Allan, Omali, Denis, Aarnoutse, Rob, Lamorde, Mohammed, Dooley, Kelly E, Sloan, Derek James, Sekaggya-Wiltshire, Christine, Denti, Paolo
Format Journal Article
LanguageEnglish
Published United States 15.11.2023
Subjects
Adult
Anti-HIV Agents - pharmacokinetics
Antibiotics, Antitubercular - pharmacokinetics
Antitubercular Agents - pharmacokinetics
Antitubercular Agents - therapeutic use
Benzoxazines - pharmacokinetics
Benzoxazines - therapeutic use
Cyclopropanes
HIV Infections - drug therapy
Humans
Rifampin - pharmacokinetics
Tuberculosis - drug therapy
Uganda
Uganda
pharmacokinetics
rifampicin
top-up capsule
high-dose
bioavailability
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Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:0066-4804
1098-6596
1098-6596
DOI:10.1128/AAC.00431-23