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Antimicrob Agents Chemother. 2015 Oct 19;60(1):617-20. doi: 10.1128/AAC.01195-15.

Effect of SLCO1B1 Polymorphisms on Rifabutin Pharmacokinetics in African HIV-Infected Patients with Tuberculosis.

Author information

  • 1School of Pharmacy, The University of Queensland, Woolloongabba, Australia s.hennig@uq.edu.au.
  • 2TB Research Unit, Medical Research Council, Durban, South Africa.
  • 3Biostatistics Unit, Medical Research Council, Durban, South Africa.
  • 4Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
  • 5Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
  • 6TB Research Unit, Medical Research Council, Durban, South Africa KwaZulu-Natal Research Institute for Tuberculosis & HIV (K-RITH), Nelson Mandela School of Medicine, Durban, South Africa.

Abstract

Rifabutin, used to treat HIV-infected tuberculosis, shows highly variable drug exposure, complicating dosing. Effects of SLCO1B1 polymorphisms on rifabutin pharmacokinetics were investigated in 35 African HIV-infected tuberculosis patients after multiple doses. Nonlinear mixed-effects modeling found that influential covariates for the pharmacokinetics were weight, sex, and a 30% increased bioavailability among heterozygous carriers of SLCO1B1 rs1104581 (previously associated with low rifampin concentrations). Larger studies are needed to understand the complex interactions of host genetics in HIV-infected tuberculosis patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00640887.).

PMID:
26482301
PMCID:
PMC4704238
DOI:
10.1128/AAC.01195-15
[PubMed - indexed for MEDLINE]
Free PMC Article
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