Related Experiment Video
Updated: May 3, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
Published on: March 28, 2017
Bedaquiline metabolism: enzymes and novel metabolites
1Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (K.L., J.L., S.L., W.X., X.M.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas (F.L., K.D.).
Abstract:
Bedaquiline is a recently approved drug for the treatment of multidrug-resistant tuberculosis. Adverse cardiac and hepatic drug reactions to bedaquiline have been noted in clinical practice. The current study investigated bedaquiline metabolism in human hepatocytes using a metabolomic approach. Bedaquiline N-demethylation via CYP3A4 was confirmed as the major pathway in bedaquiline metabolism. In addition to CYP3A4, we found that both CYP2C8 and CYP2C19 contributed to bedaquiline N-demethylation. The Km values of CYP2C8, CYP2C19, and CYP3A4 in bedaquiline N-demethylation were 13.1, 21.3, and 8.5 µM, respectively. We also identified a novel metabolic pathway of bedaquiline that produced an aldehyde intermediate. In summary, this study extended our knowledge of bedaquiline metabolism, which can be applied to predict and prevent drug-drug interactions and adverse drug reactions associated with bedaquiline.
Related Concept Videos
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Drug Metabolism: Phase II Reactions
Drug Biotransformation: Overview
Drug Biotransformation: Overview
Pharmacokinetics in Pediatric Patients: Drug Metabolism
Phase II Reactions: Acetylation Reactions
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...

