Mechanistic modeling of a magnetic marker monitoring study linking gastrointestinal tablet transit, in vivo drug release, and pharmacokinetics.
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.
Bergstrand
M
M
Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. martin.bergstrand@farmbio.uu.se
Söderlind
E
E
Weitschies
W
W
Karlsson
M O
MO
D000284:Administration, Oral; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism*; D018592:Cross-Over Studies; D005772:Gastrointestinal Transit / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008280:Magnetics; D008390:Markov Chains; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D013607:Tablets
D015415:Biomarkers; D004364:Pharmaceutical Preparations; D013607:Tablets