Effects of CYP3A5 genetic polymorphism on the pharmacokinetics of tamsulosin in subjects with with CYP2D6*10/*10

Purpose: Tamsulosin is a selective α₁-adrenoceptor antagonist and is primarily used for the treatment of lower urinary tract symptoms that are suggestive of benign prostatic hyperplasia (BPH). CYP3A4 and CYP2D6 are major metabolic enzymes responsible for the biotransformation of tamsulosin. It is reported that CYP3A5, one of highly polymorphic CYP450 isozyme, is considered to have similar substrate specificity with CYP3A4. We investigated the effects of CYP3A5 genetic polymorphism on the pharmacokinetics of tamsulosin when the CYP2D6 activity was decreased.

Methods: Ten healthy subjects genotyped as homozygous for the CYP2D6*10 alleles were recruited and they were divided into two groups according to CYP3A5 genotype, CYP3A5 expressors (CYP3A5*1/*1 or CYP3A5*1/*3, n=4) and CYP3A5 non-expressors (CYP3A5*3/*3, n=6). After overnight fasting, each subject received a single oral dose of 0.2 mg tamsulosin. Blood samples were collected up to 48 hr after drug intake in each phase, and plasma concentrations of tamsulosin were determined by using LC-MS/MS system.

Results: C_max and AUC values of tamsulosin in CYP3A5 expressors and non-expressors were not significantly different. AUC_inf of tamsulosin in each genotype group was 88.2 ± 25.2 ng·hr/mL and 80.4 ± 10.4 ng·hr/mL, respectively. Although 1.3-fold longer half-life (t_1/2) of tamsulosin was observed in CYP3A5 expressors compared with that in CYP3A5 non-expressors, these difference was not also statistically significant.

Conclusion: CYP3A5 genetic polymorphism is not likely to affect the pharmacokinetics of tamsulosin.