Effect of High-Fat Diets on the Pharmacokinetics of Bedaquiline Fumarate Tablet: A Trial in Healthy Chinese Participants.

Abstract

Bedaquiline is employed to treat multidrug-resistant and extensive drug-resistant tuberculosis by inhibiting the proton pump of adenosine triphosphate synthase in Mycobacterium tuberculosis. This study aims to investigate the effect of high-fat diets on the pharmacokinetics of bedaquiline through a single-center, open-label, randomized trial in healthy Chinese participants. Bedaquiline fumarate tablets were administered at a dosage of 100 mg under both fasted conditions and high-fat diet conditions. The concentrations were determined using liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated using a noncompartmental model. The high-fat diet group showed a maximum plasma concentration that exceeded that of the fasted group by more than 4-fold and an area under the concentration-time curve from time 0 to the last measurable point that was more than twice as high. Moreover, compared to the fasted group, the high-fat diet group exhibits significantly lower levels of apparent clearance, indicating that the high-fat diet markedly enhances the rate and extent of gastrointestinal absorption of bedaquiline. To optimize drug bioavailability and absorption and ensure safety, the administration of bedaquiline with food is recommended in accordance with clinical usage guidelines and expert consensus.