European Journal of Clinical Pharmacology

, Volume 74, Issue 11, pp 1417–1426 | Cite as

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 BaeEmail author
  • Yun Jeong LeeEmail author
  • Seok-Yong LeeEmail author



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.


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.


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.


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.


Cilostazol CYP2C19 CYP3A5 Genetic polymorphism Pharmacokinetics 


Funding information

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2016R1A2B4007381).

Compliance with ethical standards

All subjects provided verbal and written informed consent. This study was performed in accordance with the guidelines of the Declaration of Helsinki and was approved by the Institutional Ethics Committee of Sungkyunkwan University, Suwon, Korea.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2018_2522_MOESM1_ESM.pptx (5.6 mb)
ESM 1 (PPTX 5696 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of PharmacySungkyunkwan UniversitySuwonRepublic of Korea
  2. 2.College of PharmacyDongguk University-SeoulGoyangRepublic of Korea
  3. 3.College of PharmacyKeimyung UniversityDaeguRepublic of Korea
  4. 4.College of PharmacyDankook UniversityCheonanRepublic of Korea

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