Application of the convection-dispersion equation to modelling oral drug absorption.
Models of systemic drug absorption after oral administration are frequently based on a direct or a delayed first-order rate process. In practice, the use of the first-order approach to predict drug concentrations in blood plasma frequently yields a considerable mismatch between predicted and measured concentration profiles. This is particularly true for the upswing of the plasma concentration after oral administration. The current investigation explores an alternative model to describe the absorption rate based on the convection-dispersion equation describing the transport of chemicals through the GI tract. This equation is governed by two parameters, transport velocity and dispersion coefficient. One solution of this equation for a specific set of initial and boundary conditions was used to model absorption of paracetamol in a 22-year-old man after oral administration. The GI-tract passage rate in this subject was influenced by co-administration of drugs that stimulate or delay gastric emptying. The transport-limited absorption function is more accurate in describing the plasma concentration versus time curve after oral administration than the first-order model. Additionally, it provides a mechanistic explanation for the observed curve through the differences in GI-tract passage rate.
Freijer
Jan I
JI
LAP & P Consultants BV, Archimedesweg 31, 2333 CM Leiden, The Netherlands. jan.freijer@nl.astellas.com
Post
Teun M
TM
Ploeger
Bart A
BA
DeJongh
Joost
J
Danhof
Meindert
M
D000082:Acetaminophen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D008954:Models, Biological; D016011:Normal Distribution; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen