Effect of CYP2D6 polymorphism on Tamoxifen pharmacokinetic in Thai breast cancer patients

Abstract

The purposes of this study were to explore CYP2D6*10 allele frequency in Thai breast cancer patients and compare tamoxifen and its metabolites plasma concentration between patients with CYP2D6*1 and CYP2D6*10 alleles. A prospective clinical study was performed, data was collected at the breast cancer surgery outpatient clinic of Phramongkutklao hospital, Bangkok. Genotyping of CYP2D6 was analyzed in 67 breast cancer patients. The frequency of CYP2D6*10/10, CYP2D6*1/10, and CYP2D6*1/1 was 29.9 %, 37.3%, and 32.8 %, respectively. Our results showed that the steady-state plasma concentrations of tamoxifen and its metabolites (endoxifen and N-desmethyltamoxifen among 59 patients with three CYP2D6 genotypes were significantly different (P = 0.045). The plasma concentrations of endoxifen in patients carrying CYP2D6*10/*10 were lower than those with CYP2D6 1/*10 and CYP2D6 1/*1 (9.62 ng/ml vs 15.67 ng/ml vs 21.55 ng/ml, respectively). In addition, the plasma concentrations of N-desmethyltamoxifen and tamoxifen among three CYP2D6 genotypes were also significantly different (P= 0.020, P= 0.027, respectively).