Zhang Wenpeng, Li Yanyan, Zou Peng, Wu Man, Zhang Zhenqing, Zhang Tao
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
School of Science and Humanities, Husson University, Bangor, Maine, USA.
AAPS J. 2016 Jul;18(4):830-43. doi: 10.1208/s12248-016-9928-8. Epub 2016 May 16.
Accumulating evidence from the last decade has shown that many pharmaceutical excipients are not pharmacologically inert but instead have effects on metabolic enzymes and/or drug transporters. Hence, the absorption, distribution, metabolism, and elimination (ADME) of active pharmaceutical ingredients (APIs) may be altered due to the modulation of their metabolism and transport by excipients. The impact of excipients is a potential concern for Biopharmaceutics Classification System (BCS)-based biowaivers, particularly as the BCS-based biowaivers have been extended to class 3 drugs in certain dosage forms. The presence of different excipients or varying amounts of excipients between formulations may result in bio-inequivalence. The excipient impact may lead to significant variations in clinical outcomes as well. The aim of this paper is to review the recent findings of excipient effects on gastrointestinal (GI) absorption, focusing on their interactions with the metabolic enzymes and transporters in the GI tract. A wide range of commonly used excipients such as binders, diluents, fillers, solvents, and surfactants are discussed here. We summarized the reported effects of those excipients on GI tract phase I and phase II enzymes, uptake and efflux transporters, and relevant clinical significance. This information can enhance our understanding of excipient influence on drug absorption and is useful in designing pharmacokinetic studies and evaluating the resultant data.
过去十年积累的证据表明，许多药物辅料并非无药理活性，而是会对代谢酶和/或药物转运体产生影响。因此，活性药物成分（API）的吸收、分布、代谢和排泄（ADME）可能会因辅料对其代谢和转运的调节作用而发生改变。辅料的影响是基于生物药剂学分类系统（BCS）的生物豁免的一个潜在问题，特别是因为基于BCS的生物豁免已扩展到某些剂型的3类药物。不同辅料的存在或不同制剂之间辅料用量的差异可能导致生物不等效。辅料的影响也可能导致临床结果出现显著差异。本文的目的是综述辅料对胃肠道（GI）吸收影响的最新研究结果，重点关注它们与胃肠道代谢酶和转运体的相互作用。本文讨论了多种常用辅料，如粘合剂、稀释剂、填充剂、溶剂和表面活性剂。我们总结了这些辅料对胃肠道I相和II相酶、摄取和外排转运体的报道影响以及相关临床意义。这些信息可以加深我们对辅料对药物吸收影响的理解，有助于设计药代动力学研究并评估所得数据。
