title: Improvement of trospium-specific absorption models for fasted and fed states in humans.
abstract: The purpose of this study was to mechanistically interpret the oral absorption pattern of trospium in fasted and fed states by means of gastrointestinal simulation technology. A drug absorption model was built on the basis of experimental data. According to the generated model, low permeability across the intestinal epithelium, delayed gastric emptying time and a prolonged residence time in the small intestine are the key factors governing trospium absorption in the fasted state. Furthermore, in silico modelling provided a plausible explanation of the pronounced reduction in the oral bioavailability of trospium when administered with food. The simulation results support the decreased dissolution in viscous medium, and the reduced drug permeability in the fed state as the predominant mechanisms for the food effect on trospium absorption.
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, Belgrade, Serbia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Cvijić
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
mesh_terms: D001561:Benzilates / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000378:metabolism*; D018565:Food-Drug Interactions; D005746:Gastric Emptying / Q000187:drug effects; D065569:Gastrointestinal Absorption / Q000187:drug effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009662:Nortropanes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013997:Time Factors; D064804:Urological Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D001561:Benzilates; D009662:Nortropanes; D064804:Urological Agents; C003330:trospium chloride
keywords: absorption simulation; bile salts; food effect; trospium; viscosity