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

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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Funding

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).

Author information

Author notes

  1. Hye-In Lee, Ji-Young Byeon and Young-Hoon Kim contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea

    Hye-In Lee, Ji-Young Byeon, Young-Hoon Kim, Choong-Min Lee, Choon-Gon Jang & Seok-Yong Lee

  2. College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Republic of Korea

    Chang-Ik Choi

  3. College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea

    Jung-Woo Bae

  4. College of Pharmacy, Dankook University, Cheonan, 31116, Republic of Korea

    Yun Jeong Lee

Authors
  1. Hye-In Lee
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  2. Ji-Young Byeon
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  3. Young-Hoon Kim
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  4. Choong-Min Lee
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Corresponding authors

Correspondence to Jung-Woo Bae, Yun Jeong Lee or Seok-Yong Lee.

Ethics declarations

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.

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The authors declare that they have no conflict of interest.

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Lee, HI., Byeon, JY., Kim, YH. et al. Effects of CYP2C19 and CYP3A5 genetic polymorphisms on the pharmacokinetics of cilostazol and its active metabolites. Eur J Clin Pharmacol 74, 1417–1426 (2018). https://doi.org/10.1007/s00228-018-2522-5

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  • DOI: https://doi.org/10.1007/s00228-018-2522-5

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