Pharmacogenetics and Pharmacokinetics of Tamoxifen in a Zimbabwean breast cancer cohort

• DOI: 10.22541/au.168081129.93760392/v1
• Publication Date: 2023-04-06T20:01:37Z
• Authors: Bianza Mbavha; Roslyn Thelingwani; Zedias Chikwambi; Anna Nyakabau; Collen Masimirembwa
• Keywords: Zimbabwe; Tamoxifen; Cytochrome P-450 CYP2D6; Antineoplastic Agents, Hormonal; Genotype; Pharmacogenetics; Tandem Mass Spectrometry; Humans; Female; Breast Neoplasms; Chromatography, Liquid

Tamoxifen is the most used hormonal therapy for estrogen receptor positive breast cancer. CYP2D6 main enzyme in metabolic pathway of tamoxifen to endoxifen. Variations endoxifen plasma concentrations are associated with polymorphisms. This study aimed determine association between polymorphisms and a cohort Zimbabwean cancer patients (n = 40). TaqMan genotyping copy number assays were done genotypes. metabolites quantitated using LC-MS/MS. The population had high frequencies reduced function alleles, *17 (15%) *29 (18%). median concentration was 4.78 ng/ml 55% patients, mostly intermediate metabolizers below therapeutic threshold 5.97 ng/ml. phenotypes activity scores significantly (p 0.0151) N-desmethyl ratios 0.0006).