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

Antimicrob Agents Chemother. 2015 Oct 19;60(1):617-20. doi: 10.1128/AAC.01195-15. Print 2016 Jan.

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.).

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / blood
  • Antitubercular Agents / pharmacokinetics*
  • Area Under Curve
  • CD4 Lymphocyte Count
  • Coinfection
  • Ethambutol / administration & dosage
  • Female
  • Gene Expression
  • HIV Infections / pathology
  • HIV Infections / virology
  • Humans
  • Isoniazid / administration & dosage
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Monte Carlo Method
  • Organic Anion Transporters / genetics*
  • Organic Anion Transporters / metabolism
  • Polymorphism, Single Nucleotide*
  • Pyrazinamide / administration & dosage
  • Rifabutin / administration & dosage
  • Rifabutin / blood
  • Rifabutin / pharmacokinetics*
  • Rifampin / administration & dosage
  • Sex Factors
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / pathology

Substances

  • Antitubercular Agents
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Rifabutin
  • Pyrazinamide
  • Ethambutol
  • Isoniazid
  • Rifampin

Associated data

  • ClinicalTrials.gov/NCT00640887