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

TitleEffect of SLCO1B1 Polymorphisms on Rifabutin Pharmacokinetics in African HIV-Infected Patients with Tuberculosis.
Publication TypeJournal Article
Year of Publication2015
AuthorsHennig S, Naiker S, Reddy T, Egan D, Kellerman T, Wiesner L, Owen A, McIlleron H, Pym A
JournalAntimicrob Agents Chemother
Volume60
Issue1
Pagination617-20
Date Published2015 Oct 19
ISSN1098-6596
KeywordsAdult, Antitubercular Agents, Area Under Curve, CD4 Lymphocyte Count, Coinfection, Ethambutol, Female, Gene Expression, HIV Infections, Humans, Isoniazid, Male, Monte Carlo Method, Organic Anion Transporters, Polymorphism, Single Nucleotide, Pyrazinamide, Rifabutin, Rifampin, Sex Factors, Solute Carrier Organic Anion Transporter Family Member 1b1, Tuberculosis, Pulmonary
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.).

DOI10.1128/AAC.01195-15
Alternate JournalAntimicrob. Agents Chemother.
PubMed ID26482301
PubMed Central IDPMC4704238
Grant ListUM1 AI068634 / AI / NIAID NIH HHS / United States
G0800247 / / Medical Research Council / United Kingdom
UM1 AI106701 / AI / NIAID NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States