Bioequivalence Study of 100-mg Cilostazol Tablets in Healthy Thai Adult Volunteers

Highlights

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  Cilostazol is used in practice for the management of peripheral arterial disease.

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  A generic formulation of cilostazol was compared (C _max, AUC, T _max) with the brand-name product.

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  No statistically significant differences were found in either the bioavailability or safety profiles of the two products.

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  The generic version could increase Thai patients’ access to cilostazol.

Abstract

Background

Cilostazol is a vasodilator with anticoagulant effect for treatment of peripheral vascular disease. Cilostazol 100-mg tablet was shown to increase walking distance in this patient population.

Objective

The aim of this study was to investigate and compare the pharmacokinetic profiles and safety of Bestazol 100-mg tablet (Berlin Pharmaceutical Industry Co Ltd, Bangkok, Thailand), which is a generic formulation of cilostazol, with the original brand Pletaal 100-mg tablet (Korea Otsuka Pharmaceutical Co Ltd, Seoul, South Korea) in healthy Thai adult volunteers.

Methods

The pharmacokinetic profiles of Bestazol (test) and Pletaal (reference) 100-mg tablets were compared in a single-dose, open-label, 2-treatment, 2-period, 2-sequence, randomized crossover study in healthy Thai adult volunteers. This study was conducted at the Siriraj Clinical Research Center, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Each volunteer was initially treated according to either the test–reference or the reference–test sequence, after which each volunteer was switched to the other study sequence after a 2-week washout period. Pharmacokinetic analysis was performed using log-transformed ratios for C _max, AUC _0–last, AUC _0–∞, T _max, t _1/2, and λ _Z for both cilostazol and 3,4-dehydro-cilostazol (its active metabolite) with 90% CI. Physical examination, clinical laboratory data, vital signs, and adverse events were assessed in all participants.

Findings

A total of 28 volunteers were included in the final analysis. The ratios of the geometric mean and the 90% CI compared test to reference of cilostazol formulations and were 101.86% (90% CI, 91.88%–112.92%), 107.78% (90% CI, 99.67%–116.56%), and 110.46% (90% CI, 102.68%–118.82%) for C _max, AUC _0–last, and AUC _0–∞, respectively. The ratios of the geometric mean and the 90% CI compared test to reference of 3,4-dehydro-cilostazol and were 106.72% (95% CI, 95.31%–119.50%), 110.54% (95% CI, 101.92%–119.89%), and 107.37% (95% CI, 96.74%–119.16%) for C _max, AUC _0–last, and AUC _0–∞, respectively. No significant difference was observed between formulations for T _max. The most common adverse event was headache (51.85%), with no significant difference in incidence between the test and reference groups. No serious adverse events related to the studied drugs were reported. The findings of this study indicate these 2 cilostazol tablet formulations to be bioequivalent.

Conclusions

Bestazol 100-mg tablet was bioequivalent to Pletaal 100-mg tablet. Thus, the formulations can be used interchangeably in clinical practice.