title: Effects of CYP induction by rifampicin on tamoxifen exposure.
abstract: Tamoxifen undergoes biotransformation into several metabolites, including endoxifen. Differences in metabolism contribute to the interindividual variability in endoxifen concentrations, potentially affecting treatment efficacy. We evaluated the effects of cytochrome P450 (CYP) induction by rifampicin on the exposure levels of tamoxifen and its metabolites and found that coadministration of rifampicin resulted in markedly reduced (up to 86%, P ≤ 0.040) concentrations of tamoxifen and its metabolites. Given the extensive metabolism undergone by tamoxifen, several factors may have contributed to this effect. Similar drug-drug interactions may exist between tamoxifen and other strong CYP inducers.
authors.affiliation: Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, University Medical Center, Rotterdam, The Netherlands. l.binkhorst@erasmusmc.nl
authors.forename: L
authors.initials: L
authors.lastname: Binkhorst
authors.forename: T
authors.initials: T
authors.lastname: van Gelder
authors.forename: W J
authors.initials: WJ
authors.lastname: Loos
authors.forename: F E
authors.initials: FE
authors.lastname: de Jongh
authors.forename: P
authors.initials: P
authors.lastname: Hamberg
authors.forename: I M Ghobadi
authors.initials: IM
authors.lastname: Moghaddam-Helmantel
authors.forename: E
authors.initials: E
authors.lastname: de Jonge
authors.forename: A
authors.initials: A
authors.lastname: Jager
authors.forename: C
authors.initials: C
authors.lastname: Seynaeve
authors.forename: R H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.forename: R H J
authors.initials: RH
authors.lastname: Mathijssen
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001711:Biotransformation / Q000187:drug effects / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D012293:Rifampin / Q000493:pharmacokinetics*; D013629:Tamoxifen / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D013629:Tamoxifen; D003577:Cytochrome P-450 Enzyme System; D012293:Rifampin