Impact of lopinavir-ritonavir or nevirapine on bedaquiline exposures and potential implications for patients with tuberculosis-HIV coinfection.

ABSTRACT: Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patients are available. Plasma concentrations of bedaquiline and its M2 metabolite after single doses were obtained from interaction studies with nevirapine or LPV/r in healthy volunteers. The antiretrovirals' effects on bedaquiline and M2 pharmacokinetics were assessed by nonlinear mixed-effects modeling. Potential dose adjustments were evaluated with simulations. No significant effects of nevirapine on bedaquiline pharmacokinetics were identified. LPV/r decreased bedaquiline and M2

SUBMITTER: Svensson EM 

PROVIDER: S-EPMC4249405 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature