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Improvement of trospium‐specific absorption models for fasted and fed states in humans
Author(s) -
Cvijić Sandra,
Langguth Peter
Publication year - 2014
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.1911
Subject(s) - bioavailability , absorption (acoustics) , gastric emptying , pharmacokinetics , pharmacology , chemistry , drug , permeability (electromagnetism) , medicine , materials science , biochemistry , stomach , composite material , membrane
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. Copyright © 2014 John Wiley & Sons, Ltd.