Pharmacokinetics of Tamoxifen and Its Major Metabolites and the Effect of the African Ancestry Specific CYP2D6*17 Variant on the Formation of the Active Metabolite, Endoxifen.

ABSTRACT: Tamoxifen (TAM) is widely used in the treatment of hormone receptor-positive breast cancer. TAM is metabolized into the active secondary metabolite endoxifen (ENDO), primarily by CYP2D6. We aimed to investigate the effects of an African-specific CYP2D6 variant allele, CYP2D6*17, on the pharmacokinetics (PK) of TAM and its active metabolites in 42 healthy black Zimbabweans. Subjects were grouped based on CYP2D6 genotypes as CYP2D6*1/*1 or *1/*2 or *2/*2 (CYP2D6*1 or *2), CYP2D6*1/*17 or 2*/*17, and CYP2D6*17/*17. PK parameters for TAM and three metabolites were determined. The pharmacokinetics of ENDO showed statistically significant differences among the three groups. The mean ENDO AUC_0-∞ in CYP2D6*17/*17 subjects was 452.01 (196.94) h·*ng/mL, and the

SUBMITTER: Kanji CR 

PROVIDER: S-EPMC9961245 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature