Unexpectedly low drug exposures among Ugandan patients with TB and HIV receiving high-dose rifampicin-Reference-Cited by-同舟云学术

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

Published:2023-11-15 Issue:11 Volume:67 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Kengo Allan¹^ORCID,Gausi Kamunkhwala¹,Nabisere Ruth²,Musaazi Joseph²,Buzibye Allan²,Omali Denis²,Aarnoutse Rob³,Lamorde Mohammed²,Dooley Kelly E.⁴,Sloan Derek James⁵,Sekaggya-Wiltshire Christine²,Denti Paolo¹

Affiliation:

1. Department of Medicine, Division of Clinical Pharmacology, University of Cape Town , Cape Town, South Africa

2. Infectious Disease Institute, College of Health Sciences, Makerere University , Kampala, Uganda

3. Department of Pharmacy, Radboud university medical center , Nijmegen, the Netherlands

4. Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Centre , Nashville, Tennessee, USA

5. Division of Infection and Global Health, School of Medicine, University of St. Andrews , Scotland, United Kingdom

Abstract

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.

Funder

EC | H2020 | ERA-LEARN | European and Developing Countries Clinical Trials Partnership

HHS | NIH | NIH Office of the Director

Scottish Funding Council

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/aac.00431-23

Reference31 articles.

1. Comparing the Efficacy of Drug Regimens for Pulmonary Tuberculosis: Meta-analysis of Endpoints in Early-Phase Clinical Trials

2. Increased bactericidal activity but dose-limiting intolerability at 50 mg·kg−1 rifampicin

3. Clinical Pharmacokinetics of Rifampicin

4. Roles of rifampicin in drug-drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor

5. Pharmacokinetic Interactions with Rifampicin