Bedaquiline

General information

Bedaquiline is a diarylquinoline (previously referred to as TMC207 and before that R207910) that has many characteristics, both in vitro and in vivo, that make it a very attractive antituberculosis drug candidate [ ]. It is very potent in vitro against both multidrug-resistant and drug-susceptible strains of Mycobacterium tuberculosis [ , ]. It inhibits mycobacterial F1F0 proton ATP [ ]. Bedaquiline was more active than isoniazid and rifampicin in a mouse model and shortened therapy from 4 months to 2 months in mice with established infection. In phase I studies in humans tolerability was good and the pharmacokinetics were linear over the dose range studied. In a phase 1 study of multiple ascending doses there was accumulation, with increases in the AUC by a factor of about two between day 1 and day 14. The effective half-life was of the order of 24 hours.