title: The Effects of Pharmaceutical Excipients on Gastrointestinal Tract Metabolic Enzymes and Transporters-an Update.
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.
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Science and Humanities, Husson University, Bangor, Maine, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: CDER/OPQ, Food and Drug Administration (FDA), Silver Springs, Maryland, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, Husson University, Bangor, Maine, USA. zhangt@husson.edu.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
mesh_terms: D001702:Biopharmaceutics / Q000145:classification*; D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000008:administration & dosage*; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations
chemical_list: D005079:Excipients; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations
keywords: absorption; metabolic enzyme; pharmaceutical excipient; pharmacokinetics; transporter