Population Pharmacokinetic Analysis of Bedaquiline-Clarithromycin for Dose Selection Against Pulmonary Nontuberculous Mycobacteria Based on a Phase 1, Randomized, Pharmacokinetic Study.

ABSTRACT: Based on the in vitro profile of bedaquiline against mycobacterial species, it is being investigated for clinical efficacy against pulmonary nontuberculous mycobacteria (PNTM). Being a cytochrome P450 3A substrate, pharmacokinetic interactions of bedaquiline are anticipated with clarithromycin (a cytochrome P450 3A inhibitor), which is routinely used in pulmonary nontuberculous mycobacteria treatment. This phase 1, randomized, crossover study assessed the impact of steady-state clarithromycin (500 mg every 12 hours for 14 days) on the pharmacokinetics of bedaquiline and its metabolite (M2) after single-dose bedaquiline (100 mg; n  =  16). Using these data, population pharmacokinetic modeling and simulation analyses were performed to determine the effect of clarithromycin on steady-state be

SUBMITTER: Kurosawa K 

PROVIDER: S-EPMC8518967 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature