Effects of CYP2D6 and CYP3A5 genetic polymorphisms on steady-state pharmacokinetics and hemodynamic effects of tamsulosin in humans

Kyoung Ah Kim, In Bae Park, Ji-Young Park

Research output: Contribution to journalArticle

Abstract

Purpose: Tamsulosin is one of the most potent drugs currently available to treat benign prostatic hyperplasia. Cytochrome P450 (CYP) 2D6 and CYP3A are the two major enzymes responsible for tamsulosin metabolism. The purpose of this study was to evaluate the effects of CYP2D6 and CYP3A5 genetic polymorphisms on the pharmacokinetics and hemodynamic effects of tamsulosin in humans. Methods: Twenty-nine male subjects were enrolled and their CYP2D6 (*2,*4,*5,*10,*14,*21,*41, and *xN) and CYP3A5 (*5) genotypes were screened. Tamsulosin was administered daily for 6 days to assess its steady-state pharmacokinetics and hemodynamic effects according to CYP2D6 and CYP3A5 genotypes. Results: CYP2D6 group 3 (with genotype *10/*10 or *5/*10) exhibited higher plasma levels than CYP2D6 group 1 (with genotype *1/*1,*1/*2,*1/*2xN, or *2/*10xN) or CYP2D6 group 2 (with genotype *1/*10,*1/*41, or *2/*5) (trough concentrations for groups 1, 2, and 3: 1.3, 1.8, and 3.8 ng/mL, respectively [P < 0.001]; peak concentrations for groups 1, 2, 3: 8.3, 10.0, and 13.8 ng/mL, respectively [P < 0.005]). Similarly, CYP2D6 genotypes influenced the hemodynamic effects of tamsulosin based on systolic and diastolic blood pressures. However, the CYP3A5*3 polymorphism did not affect tamsulosin plasma levels and its hemodynamic effects. Conclusion: The CYP2D6 but not the CYP3A5 genetic polymorphisms affected the pharmacokinetics and the hemodynamic effects of tamsulosin.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalEuropean Journal of Clinical Pharmacology
DOIs
Publication statusAccepted/In press - 2018 Jun 13

Keywords

  • CYP2D6
  • CYP3A5
  • Hemodynamics
  • Pharmacogenetics
  • Pharmacokinetics
  • Single-nucleotide polymorphism
  • Tamsulosin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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