Effects of Cilostazol on the Pharmacokinetics of Nifedipine After Oral and Intravenous Administration in Rats
- Authors: Lee C.1, Choi J.2, Choi D.3
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Affiliations:
- Department of Medical Management, Chodang University
- College of Pharmacy, Chosun University
- Department of Internal Medicine, College of Medicine, Chosun University
- Issue: Vol 51, No 9 (2017)
- Pages: 748-755
- Section: Article
- URL: https://journals.rcsi.science/0091-150X/article/view/244787
- DOI: https://doi.org/10.1007/s11094-017-1686-0
- ID: 244787
Cite item
Abstract
The purpose of this study was to investigate the effects of cilostazol on the bioavailability and pharmacokinetics of nifedipine and its main metabolite, dehydronifedipine, in rats. The pharmacokinetic parameters of nifedipine and dehydronifedipine were determined following oral and intravenous administration of nifedipine (1.5 and 6.0 mg ・ kg-1) in rats. Cilostazol inhibited CYP3A4 enzyme activity at a 50% inhibitory concentration (IC50) of 4.1 μM. The areas under the plasma concentration–time curve (AUC0-∞) and the peak concentration (Cmax) of nifedipine were significantly increased, respectively, in the presence of cilostazol compared to that in the control. The total body clearance (CL/F) was significantly decreased by cilostazol. Consequently, the absolute bioavailability (AB) of nifedipine with cilostazol was significantly higher than that in the control. The metabolite to parent AUC ratio (MR) in the presence of cilostazol was significantly decreased compared to that in the control. The AUC0-∞ of intravenous nifedipine was significantly increased with cilostazol compared to that in the control. The increased bioavailability of nifedipine in rats can be mainly due to the inhibition of CYP3A4-mediated metabolism in the small intestine and/or liver by cilostazol. In addition, the reduction of CL/F of nifedipine by cilostazol may also be a factor.
Keywords
About the authors
Chong-Ki Lee
Department of Medical Management, Chodang University
Email: dhchoi@chosun.ac.kr
Korea, Republic of, Mooan, Chunnam, 534-701
Jun-Shik Choi
College of Pharmacy, Chosun University
Email: dhchoi@chosun.ac.kr
Korea, Republic of, Gwangju, 501-759
Dong-Hyun Choi
Department of Internal Medicine, College of Medicine, Chosun University
Author for correspondence.
Email: dhchoi@chosun.ac.kr
Korea, Republic of, 309 Pilmundaero, Dong-gu, Gwangju, 501-759