依巴斯汀片生物等效性研究的一般设计要求及相关考虑

General design requirements and relevant considerations on bioequivalence study of ebastine tablets

依巴斯汀是第二代长效、高选择性的组胺H1受体阻断药,其片剂由西班牙Almirall Prodesfarma公司研发,于1989年12月在西班牙首次获批上市,适用于伴有或不伴有过敏性结膜炎的过敏性鼻炎(季节性和常年性)、慢性特发性荨麻疹等的对症治疗。依巴斯汀片口服给药后,主要成分依巴斯汀被快速吸收,大部分在肝中代谢为活性代谢产物卡瑞斯汀,原形药物依巴斯汀的血浆浓度远低于卡瑞斯汀,且个体内变异较大。因此,在生物等效性研究中需对检测物质、生物等效性评价等方面进行充分考虑与合理设计。本文结合依巴斯汀片的药代动力学特征,及其仿制药在国内、外上市前所开展的生物等效性研究情况,讨论了本品生物等效性研究的一般设计要求及相关考虑,以期为国内仿制药的研发提供参考。

Ebastine is a second-generation long-acting and highly selective antagonist of the histamine H1 receptor. Its tablets were developed by Almirall Prodesfarma,a Spanish pharmaceuticals company.Ebastine tablets are intended for the symptomatic treatment of urticarial,seasonal and nonseasonal allergic rhinitis, with or without allergic conjunctivitis. After oral administration,ebastine is rapidly absorbed from the gastrointestinal tract, and is largely converted to the pharmacologically active metabolite carebastine. The parent compound ebastine has a lower plasma concentration and higher variability in pharmacokinetics than carebastine. Therefore, in a bioequivalence study,it is necessary to reasonably design and give full consideration to substance detection,bioequivalence evaluation and so on. This paper mainly discusses the general design requirements and relevant considerations of the bioequivalence studies regarding ebastine tablets,based on its pharmacokinetics characteristics and the bioequivalence studies in the domestic and overseas,in order to provide reference for the research and development of generic drugs of ebastine in China.