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The Effects of Pharmaceutical Excipients on Gastrointestinal Tract Metabolic Enzymes and Transporters—an Update

  • Review Article
  • Theme: Effects of Pharmaceutical Excipients on the Function of Transporters and Cytochrome P450 in Gastrointestinal Tract and Or
  • Published:
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Abstract

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.

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    Authors and Affiliations

    1. State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China

      Wenpeng Zhang, Man Wu & Zhenqing Zhang

    2. School of Science and Humanities, Husson University, Bangor, Maine, USA

      Yanyan Li

    3. CDER/OPQ, Food and Drug Administration (FDA), Silver Springs, Maryland, USA

      Peng Zou

    4. Department of Basic Pharmaceutical Sciences, School of Pharmacy, Husson University, Bangor, Maine, USA

      Tao Zhang

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    1. Wenpeng Zhang
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    Guest Editor: Peng Zou

    Wenpeng Zhang and Yanyan Li contributed equally to this work.

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    Zhang, W., Li, Y., Zou, P. et al. The Effects of Pharmaceutical Excipients on Gastrointestinal Tract Metabolic Enzymes and Transporters—an Update. AAPS J 18, 830–843 (2016). https://doi.org/10.1208/s12248-016-9928-8

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