Effects of CYP2C19 and CYP3A5 genetic polymorphisms on the pharmacokinetics of cilostazol and its active metabolites

Hye In Lee, Ji Young Byeon, Young Hoon Kim, Choong Min Lee, Chang Ik Choi, Choon Gon Jang, Jung Woo Bae, Yun Jeong Lee, Seok Yong Lee

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Purpose: CYP3A4, CYP2C19, and CYP3A5 are primarily involved in the metabolism of cilostazol. We investigated the effects of CYP2C19 and CYP3A5 genetic polymorphisms on the pharmacokinetics of cilostazol and its two active metabolites. Methods: Thirty-three healthy Korean volunteers were administered a single 100-mg oral dose of cilostazol. The concentrations of cilostazol and its active metabolites (OPC-13015 and OPC-13213) in the plasma were determined by HPLC-MS/MS. Results: Although the pharmacokinetic parameters for cilostazol were similar in different CYP2C19 and CYP3A5 genotypes, CYP2C19PM subjects showed significantly higher AUC0-∞ for OPC-13015 and lower for OPC-13213 compared to those in CYP2C19EM subjects (P < 0.01 and P < 0.001, respectively). Pharmacokinetic differences in OPC-13015 between CYP3A5 non-expressors and expressors were significant only within CYP2C19PM subjects. The amount of cilostazol potency-adjusted total active moiety was the greatest in subjects with CYP2C19PM-CYP3A5 non-expressor genotype. Conclusion: These results suggest that CYP2C19 and CYP3A5 genetic polymorphisms affect the plasma exposure of cilostazol total active moiety. CYP2C19 plays a crucial role in the biotransformation of cilostazol.

Original languageEnglish
Pages (from-to)1417-1426
Number of pages10
JournalEuropean Journal of Clinical Pharmacology
Volume74
Issue number11
DOIs
StatePublished - 1 Nov 2018

Keywords

  • Cilostazol
  • CYP2C19
  • CYP3A5
  • Genetic polymorphism
  • Pharmacokinetics

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