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Unexpectedly low drug exposures among Ugandan patients with TB and HIV receiving high-dose rifampicin.
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.
Affiliation
  • Kengo A; Department of Medicine, Division of Clinical Pharmacology, University of Cape Town , Cape Town, South Africa.
  • Gausi K; Department of Medicine, Division of Clinical Pharmacology, University of Cape Town , Cape Town, South Africa.
  • Nabisere R; Infectious Disease Institute, College of Health Sciences, Makerere University , Kampala, Uganda.
  • Musaazi J; Infectious Disease Institute, College of Health Sciences, Makerere University , Kampala, Uganda.
  • Buzibye A; Infectious Disease Institute, College of Health Sciences, Makerere University , Kampala, Uganda.
  • Omali D; Infectious Disease Institute, College of Health Sciences, Makerere University , Kampala, Uganda.
  • Aarnoutse R; Department of Pharmacy, Radboud university medical center , Nijmegen, the Netherlands.
  • Lamorde M; Infectious Disease Institute, College of Health Sciences, Makerere University , Kampala, Uganda.
  • Dooley KE; Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Centre , Nashville, Tennessee, USA.
  • Sloan DJ; Division of Infection and Global Health, School of Medicine, University of St. Andrews , Scotland, United Kingdom.
  • Sekaggya-Wiltshire C; Infectious Disease Institute, College of Health Sciences, Makerere University , Kampala, Uganda.
  • Denti P; Department of Medicine, Division of Clinical Pharmacology, University of Cape Town , Cape Town, South Africa.
Antimicrob Agents Chemother ; 67(11): e0043123, 2023 11 15.
Article in En | MEDLINE | ID: mdl-37850737
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tuberculosis / HIV Infections / Anti-HIV Agents / Antibiotics, Antitubercular Limits: Adult / Humans Country/Region as subject: Africa Language: En Journal: Antimicrob Agents Chemother Year: 2023 Type: Article Affiliation country: South Africa
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tuberculosis / HIV Infections / Anti-HIV Agents / Antibiotics, Antitubercular Limits: Adult / Humans Country/Region as subject: Africa Language: En Journal: Antimicrob Agents Chemother Year: 2023 Type: Article Affiliation country: South Africa