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Mechanistic Modeling of a Magnetic Marker Monitoring Study Linking Gastrointestinal Tablet Transit, In Vivo Drug Release, and Pharmacokinetics
Author(s) -
Bergstrand M,
Söderlind E,
Weitschies W,
Karlsson MO
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.43
Subject(s) - pharmacokinetics , in vivo , gastrointestinal tract , pharmacology , drug , stomach , clinical pharmacology , absorption (acoustics) , physiologically based pharmacokinetic modelling , medicine , chemistry , materials science , biology , microbiology and biotechnology , composite material
Magnetic marker monitoring (MMM) is a new technique for visualizing transit and disintegration of solid oral dosage forms through the gastrointestinal (GI) tract. The aim of this work was to develop a modeling approach for gaining information from MMM studies using data from a food interaction study with felodipine extended‐release (ER) formulation. The interrelationship between tablet location in the GI tract, in vivo drug release, and felodipine disposition was modeled. A Markov model was developed to describe the tablet's movement through the GI tract. Tablet location within the GI tract significantly affected drug release and absorption through the gut wall. Food intake decreased the probability of tablet transition from the stomach, decreased the rate with which released felodipine left the stomach, and increased the fraction absorbed across the gut wall. In conclusion, the combined information of tablet location in the GI tract, in vivo drug release, and plasma concentration can be utilized in a mechanistically informative way with integrated modeling of data from MMM studies. Clinical Pharmacology & Therapeutics (2009); 86 , 1, 77–83 doi: 10.1038/clpt.2009.43