Toal Corey B, Meredith Peter A, Elliott Henry L
Department of Pharmacology, University of Toronto, Toronto, Canada.
Int J Clin Pharmacol Ther. 2012 Mar;50(3):202-17. doi: 10.5414/cp201603.
Nifedipine as a pharmacologic agent for treating hypertension and angina pectoris has been available worldwide since the early 1980's. However, the formulation of nifedipine has undergone a number of modifications over time to improve the pharmacokinetic profile and administration regimen from 3 times daily to once daily. Nifedipine Gastrointestinal Therapeutic System (GITS) is the most widely studied of the once daily formulations from both a pharmacokinetic and clinical perspective. Nifedipine GITS was registered in most major countries worldwide based on both clinical pharmacology and clinical trial data in adequately powered studies. Moreover, outcome trials in both hypertension (INSIGHT) and angina pectoris (ACTION) have been completed and published. Other once daily modified release nifedipine formulations are available in a number of countries but limited published data is available on these formulations. A Pubmed (Medline) search using the terms "nifedipine pharmacokinetics" yielded 162 articles of which 7 provided detailed pharmacokinetic values in head to head comparisons of nifedipine GITS and another once a day formulation. These published pharmacokinetic studies have failed to show that any of the other formulations is consistently bioequivalent to the reference formulation, nifedipine GITS. In addition, other Pubmed searches yielded limited data from comparative clinical studies, which show significant differences in favor of the nifedipine GITS formulation in terms of blood pressure control and activation of the sympathetic nervous system. With limited data comparing once daily formulations of nifedipine to nifedipine GITS and no data comparing between other once a day formulations, for both pharmacokinetic and therapeutic reasons, the evidence indicates that patients should not be switched between once daily formulations of nifedipine.
自20世纪80年代初以来，硝苯地平作为一种治疗高血压和心绞痛的药物已在全球范围内广泛使用。然而，随着时间的推移，硝苯地平的剂型经历了多次改进，以改善其药代动力学特征和给药方案，从每日3次给药改为每日1次给药。硝苯地平胃肠道治疗系统（GITS）是从药代动力学和临床角度进行研究最多的每日1次剂型。基于充分有力研究中的临床药理学和临床试验数据，硝苯地平GITS已在全球大多数主要国家注册。此外，高血压（INSIGHT）和心绞痛（ACTION）的结局试验均已完成并发表。其他每日1次的硝苯地平缓释剂型在许多国家都有，但关于这些剂型的已发表数据有限。使用“硝苯地平药代动力学”一词在PubMed（Medline）上进行搜索，得到162篇文章，其中7篇在硝苯地平GITS与另一种每日1次剂型的直接比较中提供了详细的药代动力学值。这些已发表的药代动力学研究未能表明任何其他剂型与参比剂型硝苯地平GITS始终具有生物等效性。此外，其他PubMed搜索从比较临床研究中获得的数据有限，这些研究表明，在血压控制和交感神经系统激活方面，硝苯地平GITS剂型具有显著优势。由于将硝苯地平每日1次剂型与硝苯地平GITS进行比较的数据有限，且没有其他每日1次剂型之间比较的数据，出于药代动力学和治疗方面的原因，有证据表明，患者不应在硝苯地平的每日1次剂型之间换药。
