Transl Clin Pharmacol.  2016 Dec;24(4):183-188. 10.12793/tcp.2016.24.4.183.

Pharmacokinetic characteristics of cilostazol 200 mg controlled-release tablet compared with two cilostazol 100 mg immediate-release tablets (Pletal) after single oral dose in healthy Korean male volunteers

Affiliations
  • 1Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea. boniii@cnu.ac.kr
  • 2Korea United Pharm.Inc., Seoul 06116, Republic of Korea.
  • 3Caleb Multilab Inc., Seoul 06745, Republic of Korea.
  • 4Clinical Trials Center, Chungnam National University Hospital, Daejeon 35015, South Korea.
  • 5Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.

Abstract

Cilostazol controlled-release (CR) tablets have recently been developed by Korea United Pharm (Seoul, Korea). The tablets use a patented double CR system, which improves drug compliance by allowing "once daily" administration and reduces adverse events by sustaining a more even plasma concentration for 24 h. We conducted an open, randomized, two-period, two-treatment, crossover study to compare the pharmacokinetic (PK) characteristics and tolerability of cilostazol when administered to healthy Korean male volunteers as CR or immediate release (IR) tablets (Pletal, Korea Otsuka Pharmaceutical Co., Gyeonggi-do, Korea). Each volunteer was randomly allocated to receive a single tablet of cilostazol CR (200 mg) or two tablets of cilostazol IR (100 mg) with a 7-day washout period between treatments. Plasma cilostazol, OPC-13015 (3,4-dehydrocilostazol), and OPC-13213 (4'-trans-hydroxycilostazol) were assayed using liquid chromatography-tandem mass spectrometry for PK analysis. Thirty participants completed the study with no clinically relevant safety issues. The peak concentrations (C(max), mean ± SD) of cilostazol CR and cilostazol IR were 1414.6 ± 49.3 and 1413.1 ± 35.2 ng/mL, respectively, and the areas under the plasma concentration-time curve from 0 to the last concentration (AUC(last)) were 23928.7 ± 65.9 and 25312.0 ± 62.6 ng·h/mL, respectively. The geometric mean ratios (cilostazol CR/cilostazol IR, GMR) of the C(max) and AUC(last) values were 1.001 (90% CI: 0.822, 1.220) and 0.945 (90% CI: 0.814, 1.098), respectively. The frequencies of adverse events were similar. The present study showed that cilostazol PK and tolerability were comparable when administered to healthy Korean men, regardless of whether administered as cilostazol CR or IR.

Keyword

Cilostazol; OPC-13015; OPC-13213; bioequivalence; pharmacokinetics

MeSH Terms

Compliance
Cross-Over Studies
Gyeonggi-do
Humans
Korea
Male*
Mass Spectrometry
Pharmacokinetics
Plasma
Tablets*
Therapeutic Equivalency
Volunteers*
Tablets

Figure

  • Figure 1. Disposition of the study participants.

  • Figure 2. Mean plasma concentration–time profiles of cilostazol (A), OPC13015(3,4-dehydrocilostazol) (B) and OPC13213 (4´-trans-hydroxycilostazol) (C) after oral administration of a single tablet of cilostazol CR 200 mg or two tablets of cilostazol IR 100 mg in healthy Korean male study participants (n = 30). The error bars represent standard deviation. ∗Reference drug: cilostazol 100 mg IR two tablets, test drug: cilostazol 200 mg CR one tablet.


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