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Biopharm Drug Dispos. 2014 Dec;35(9):553-8. doi: 10.1002/bdd.1911. Epub 2014 Aug 23.

Improvement of trospium-specific absorption models for fasted and fed states in humans.

Author information

1
Department of Pharmaceutical Technology and Cosmetology, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, Belgrade, Serbia.

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.

KEYWORDS:

absorption simulation; bile salts; food effect; trospium; viscosity

PMID:
25044357
DOI:
10.1002/bdd.1911
[Indexed for MEDLINE]

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