ABSTRACT
Traditionally, all patients treated with tamoxifen receive a standard dose. A number of studies claimed a clinically relevant impact of cytochrome P450 2D6 (CYP2D6) genotype on outcome, and therefore genotyping before tamoxifen therapy was advocated. Recent data showed that adequate exposure to the active metabolite endoxifen is important and that genotype only partially explains interindividual differences in endoxifen concentrations. Phenotyping approaches, as well as therapeutic drug monitoring (TDM) strategies, are now being tested to individualize tamoxifen treatment.
Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Breast Neoplasms/drug therapy , Precision Medicine/methods , Tamoxifen/administration & dosage , Antineoplastic Agents, Hormonal/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP2D6/metabolism , Female , Humans , Tamoxifen/metabolism , Treatment OutcomeABSTRACT
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.