title: Bedaquiline: a review of human pharmacokinetics and drug-drug interactions.
abstract: Bedaquiline has recently been approved for the treatment of pulmonary multidrug-resistant tuberculosis (TB) as part of combination therapy in adults. It is metabolized primarily by the cytochrome P450 isoenzyme 3A4 (CYP3A4) to a less-active N-monodesmethyl metabolite. Phase I and Phase II studies in healthy subjects and patients with drug-susceptible or multidrug-resistant TB have assessed the pharmacokinetics and drug-drug interaction profile of bedaquiline. Potential interactions have been assessed between bedaquiline and first- and second-line anti-TB drugs (rifampicin, rifapentine, isoniazid, pyrazinamide, ethambutol, kanamycin, ofloxacin and cycloserine), commonly used antiretroviral agents (lopinavir/ritonavir, nevirapine and efavirenz) and a potent CYP3A inhibitor (ketoconazole). This review summarizes the pharmacokinetic profile of bedaquiline as well as the results of the drug-drug interaction studies.
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium rvheesw1@its.jnj.com.
authors.forename: R P G
authors.initials: RP
authors.lastname: van Heeswijk
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA.
authors.forename: B
authors.initials: B
authors.lastname: Dannemann
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: R M W
authors.initials: RM
authors.lastname: Hoetelmans
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D064687:Diarylquinolines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D000935:Antifungal Agents; D000995:Antitubercular Agents; D000998:Antiviral Agents; D064687:Diarylquinolines; C493870:bedaquiline
keywords: CYP3A; HIV; clinical trials; tuberculosis