Chatsiricharoenkul Somruedee, Nanchaipruek Yanisorn, Manopinives Patcharaporn, Atakulreka Suparat, Niyomnaitham Suvimol
Department of Pharmacology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Siriraj Clinical Research Center, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Curr Ther Res Clin Exp. 2019 Jul 15;91:11-16. doi: 10.1016/j.curtheres.2019.06.004. eCollection 2019.
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.
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.
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, AUC, AUC T, t, and λ 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.
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, AUC, and AUC, 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, AUC, and AUC, respectively. No significant difference was observed between formulations for T. 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.
Bestazol 100-mg tablet was bioequivalent to Pletaal 100-mg tablet. Thus, the formulations can be used interchangeably in clinical practice.
西洛他唑是一种具有抗凝作用的血管扩张剂，用于治疗外周血管疾病。在该患者群体中，西洛他唑100毫克片剂可增加步行距离。
本研究旨在调查并比较泰国健康成年志愿者中，西洛他唑的仿制药Bestazol 100毫克片剂（泰国曼谷柏林制药工业有限公司）与原研品牌Pletaal 100毫克片剂（韩国首尔大冢制药株式会社）的药代动力学特征和安全性。
在泰国曼谷玛希隆大学诗里拉吉医院诗里拉吉临床研究中心，对健康泰国成年志愿者进行了一项单剂量、开放标签、双治疗、双周期、双序列、随机交叉研究，比较了Bestazol（试验）和Pletaal（参比）100毫克片剂的药代动力学特征。每位志愿者最初按照试验-参比或参比-试验顺序接受治疗，在2周的洗脱期后，每位志愿者切换到另一种研究顺序。使用对数转换后的西洛他唑及其活性代谢物3,4-脱氢西洛他唑的C、AUC、AUC T、t和λ的比值进行药代动力学分析，并给出90%置信区间。对所有参与者进行体格检查、临床实验室数据、生命体征和不良事件评估。
共有28名志愿者纳入最终分析。西洛他唑制剂试验组与参比组的几何均值比值及90%置信区间，C分别为101.86%（90%CI，91.88%-112.92%）、AUC分别为107.78%（90%CI，99.67%-116.56%）、AUC分别为110.46%（90%CI，102.68%-118.82%）。3,4-脱氢西洛他唑试验组与参比组的几何均值比值及90%置信区间，C分别为106.72%（95%CI，95.31%-119.50%）、AUC分别为110.54%（95%CI，101.92%-119.89%）、AUC分别为107.37%（95%CI，96.74%-119.16%）。两种制剂的T无显著差异。最常见的不良事件是头痛（51.85%），试验组和参比组的发生率无显著差异。未报告与研究药物相关的严重不良事件。本研究结果表明这两种西洛他唑片剂具有生物等效性。
Bestazol 100毫克片剂与Pletaal 100毫克片剂生物等效。因此，这两种制剂在临床实践中可互换使用。
