Journal of Clinical Toxicology
Open Access
ISSN: 2161-0495
+44 1478 350008
ISSN: 2161-0495
+44 1478 350008
Jee Sun Min, Jung Bae Park and Soo Kyung Bae
Catholic University of Korea, Bucheon, Republic of Korea
Posters & Accepted Abstracts: J Clin Toxicol
Cilostazol is a phosphodiesterase III inhibitor with antiplatelet activity and mainly metabolized to 3,4-dehydrocilostazol (OPC-13015) and 4�-trans-hydroxycilostazol (OPC-13213) via CYP3A4/5 and CYP2C19. Our previous IC50 shift assay revealed that both cilostazol and OPC-13015 were CYP3A time-dependent inhibitors in vitro and inhibitory effect on CYP3A4 in humans was further investigated. In this study, a randomized, open-label, multiple-dose, parallel study was conducted with 7 healthy Korean subjects and all subjects received the single oral dose of 40 mg simvastatin, a CYP3A4 probe substrate, on day 1. From day 2 to 7, the subjects were given 100 mg cilostazol 2 times per day with 12 hours interval. On day 8, the subjects received the single oral dose of 40 mg simvastatin again and plasma concentration of simvastatin on day 1 and 8 were measured using LC-MS/MS for pharmacokinetic assessment. AUC and Cmax ratio of simvastatin concentration in human plasma on Day 1 and Day 8 were 3.56 and 4.3, respectively, suggesting that cilostazol is a moderate inhibitor of CYP3A4. In conclusion, inhibitory effects of cilostazol and OPC-13015 on CYP3A4 in vitro were in line with clinical study and it is expected that significant drug-drug interaction between other CYP3A4 substrates and cilostazol may be possible.
Jee Sun Min is a graduate student with major in Pharmacology/Pharmacokinetics of The Catholic University of Korea.