Estimating human oral fraction dose absorbed: a correlation using rat intestinal membrane permeability for passive and carrier-mediated compounds.
Based on a simple tube model for drug absorption, the key parameters controlling drug absorption are shown to be the dimensionless effective permeability, P*eff, and the Graetz number, Gz, when metabolism or solubility/dissolution is not rate controlling. Estimating the Graetz number in humans and assuming that P*aq is not rate controlling give the following equation for fraction dose absorbed: F = 1 - e-2P*w. The correlation between fraction dose absorbed in humans and P*w determined from steadystate perfused rat intestinal segments gives an excellent correlation. It is of particular significance that the correlation includes drugs that are absorbed by passive and carrier-mediated processes. This indicates that P*w is one of the key variables controlling oral drug absorption and that the correlation may be useful for estimating oral drug absorption in humans regardless of the mechanism of absorption.
Amidon
G L
GL
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Sinko
P J
PJ
Fleisher
D
D
D000818:Animals; D002436:Cefatrizine / Q000493:pharmacokinetics; D002463:Cell Membrane Permeability; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D051381:Rats
D002436:Cefatrizine