Meredith Peter A, Elliott Henry L
Medicine and Therapeutics, University of Glasgow, The Western Infirmary, Glasgow, United Kingdom.
Integr Blood Press Control. 2013 Jun 25;6:79-87. doi: 10.2147/IBPC.S34803. Print 2013.
Hypertension treatment guidelines do not discriminate within drug classes and, furthermore, do not consider whether or not all of the formulations of any given drug licensed for once-daily administration can be considered to be therapeutically interchangeable. This article focuses on this issue with respect to nifedipine and the development of the gastrointestinal therapeutic system (GITS) formulation. Nifedipine GITS is regarded as the gold standard once-daily formulation of nifedipine and, as such, it is anticipated that alternative formulations will be therapeutically equivalent to nifedipine GITS. In general, this depends on demonstrating pharmacokinetic bioequivalence. This article is intended to focus attention on generic substitution and, in particular, on aspects of the scientific basis for the substitution of generic products in place of branded products. Such substitution is required for cost-saving or cost-containment reasons and is justified on the basis that the generic (substitute) drug is "therapeutically" equivalent to the branded drug. Unfortunately, there are serious shortcomings in the current methods of assessment insofar as they are typically based on statistical comparisons of average pharmacokinetic parameter values, using arbitrary comparative criteria. This article illustrates the shortcomings of the current approaches to generic substitution and concludes that, in regulatory terms, either more rigorous pharmacokinetic criteria are required or pharmacodynamic indices should be added to reinforce the regulatory criteria. Generic substitution is a balancing act but, at the moment, the cost issue is dominant. To restore the balance, equivalent efficacy must be confirmed. At present, therefore, in the absence of such regulatory rigor, the obvious course is to prefer the branded product, the therapeutic efficacy of which (including outcome benefits) has been established.
高血压治疗指南在药物类别内部不存在区别对待，而且，对于任何已获许可每日一次给药的特定药物的所有制剂是否可被视为在治疗上具有互换性也未作考量。本文围绕硝苯地平以及胃肠道治疗系统（GITS）制剂的研发来探讨这一问题。硝苯地平GITS被视为硝苯地平每日一次给药的金标准制剂，因此，预计其他制剂在治疗上应与硝苯地平GITS等效。一般而言，这取决于能否证明药代动力学生物等效性。本文旨在关注仿制药替代问题，尤其关注用仿制药替代品牌药的科学依据方面。出于节省成本或控制成本的原因需要进行这种替代，其合理性在于仿制药在“治疗”上与品牌药等效。不幸的是，当前的评估方法存在严重缺陷，因为这些方法通常基于平均药代动力学参数值的统计比较，采用的是任意的比较标准。本文阐述了当前仿制药替代方法的缺陷，并得出结论，从监管角度来看，要么需要更严格的药代动力学标准，要么应增加药效学指标以强化监管标准。仿制药替代是一种权衡之举，但目前成本问题占主导地位。为恢复平衡，必须确认等效疗效。因此，目前在缺乏这种监管严格性的情况下，显而易见的做法是优先选择品牌药，其治疗效果（包括预后益处）已经得到证实。
