Borgheini Giuseppe
Neurological and Psychiatric Department, University of Padua, and Casa di Cura Parco dei Tigli, Padua, Italy.
Clin Ther. 2003 Jun;25(6):1578-92. doi: 10.1016/s0149-2918(03)80157-1.
For the purposes of drug approval, the interchangeability of a generic drug and the corresponding brand-name drug is based on the criterion of "essential similarity," which requires that the generic drug have the same amount and type of active principle, the same route of administration, and the same therapeutic effectiveness as the original drug, as demonstrated by a bioequivalence study. However, bioequivalence and therapeutic effectiveness are not necessarily the same.
This review summarizes available data comparing the bioequivalence and therapeutic efficacy of brand-name psychoactive drugs with those of the corresponding generic products.
Relevant information was identified through searches of MEDLINE, Current Contents/Clinical Medicine, and EMBASE for English-language articles and English abstracts of articles in other languages published between 1975 and the present. The search terms used were generic drug, branded drug, safety, toxicity, adverse events, clinical efficacy, bioequivalence, bioavailability, psychoactive drugs, and excipients.
Few publications compared the bioequivalence and efficacy of brand-name and generic psychoactive drugs. Those that were identified revealed differences in the efficacy and tolerability of brand-name and generic psychoactive drugs that had not been noted in the original bioequivalence studies. Specifically, l study found that plasma levels of phenytoin were 31% lower after a switch from a brand-name to a generic product. Several controlled studies of carbamazepine showed a recurrence of convulsions after the shift to a generic formulation. After a sudden recurrence of seizures when generic valproic acid was substituted for the brand-name product, an investigation by the US Food and Drug Administration found a difference in bioavailability between the 2 formulations. Statistically significant differences in pharmacokinetic variables have been reported in favor of brand-name versus generic diazepam (P < 0.001). Finally, a case report involving paroxetine mesylate cast doubt on the tolerability and efficacy of the generic formulation.
The essential-similarity requirement should be extended to include more rigorous analyses of tolerability and efficacy in actual patients as well as in healthy subjects.
为了药物获批，仿制药与相应品牌药的可互换性基于“本质相似性”标准，这要求仿制药具有与原研药相同数量和类型的活性成分、相同的给药途径以及相同的治疗效果，这一点已通过生物等效性研究得到证实。然而，生物等效性和治疗效果不一定相同。
本综述总结了比较品牌精神活性药物与相应仿制药的生物等效性和治疗效果的现有数据。
通过检索MEDLINE、《现刊目次/临床医学》和EMBASE，查找1975年至今发表的英文文章以及其他语言文章的英文摘要，以获取相关信息。使用的检索词包括仿制药、品牌药、安全性、毒性、不良事件、临床疗效、生物等效性、生物利用度、精神活性药物和辅料。
很少有出版物比较品牌和仿制药精神活性药物的生物等效性和疗效。已确定的那些研究揭示了品牌和仿制药精神活性药物在疗效和耐受性方面的差异，而这些差异在最初的生物等效性研究中并未被注意到。具体而言，1项研究发现，从品牌药换用仿制药后，苯妥英的血浆水平降低了31%。几项卡马西平对照研究表明，改用仿制药制剂后惊厥复发。当用仿制药丙戊酸替代品牌药产品后癫痫突然复发，美国食品药品监督管理局的一项调查发现两种制剂的生物利用度存在差异。有报道称，在药代动力学变量方面，品牌地西泮相对于仿制药具有统计学显著差异（P < 0.001）。最后，1例涉及甲磺酸帕罗西汀的病例报告对仿制药制剂的耐受性和疗效提出了质疑。
本质相似性要求应扩展至包括对实际患者以及健康受试者的耐受性和疗效进行更严格的分析。
