Effect of SLCO1B1 Polymorphisms on Rifabutin Pharmacokinetics in African HIV-Infected Patients with Tuberculosis
Stefanie Hennig, Suhashni Naiker, Tarylee Reddy, Deirdre Egan, Tracy Kellerman, Lubbe Wiesner, Andrew Owen, Helen McIlleron, Alexander Pym, Stefanie Hennig, Suhashni Naiker, Tarylee Reddy, Deirdre Egan, Tracy Kellerman, Lubbe Wiesner, Andrew Owen, Helen McIlleron, Alexander Pym
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.).
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Source: PubMed