Estimate of volume/flow ratio of gastrointestinal (GI) fluids in humans using pharmacokinetic data.
Based on the mixing tank and tube models for drug absorption, the apparent absorption rate constant is shown to be related to the fraction of dose absorbed as a function of the volume/flow ratio of GI fluids. This analysis applies to drugs that are absorbed according to first-order kinetics, without limitation by dissolution rate, lumenal decomposition, or first-pass metabolism. Analysis of pharmacokinetic data of drugs that fit these criteria and are absorbed to varying extents enabled the estimation of the volume/flow ratio of GI fluids in humans; it was found to be 1.6 +/- 0.3 (SE) hr using a mixing tank model and 0.32 +/- 0.05 hr using a tube model. These findings are discussed with respect to volume and flow parameters used in the design of various types of drug absorption studies.
Macheras
P
P
Department of Pharmacy, University of Athens, Greece.
Reppas
C
C
Dressman
J B
JB
D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D004064:Digestive System / Q000378:metabolism*; D005772:Gastrointestinal Transit; D006801:Humans; D007408:Intestinal Absorption; D008432:Mathematical Computing; D008954:Models, Biological; D010599:Pharmacokinetics; D051381:Rats