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, Peff, and the Graetz number, Gz, when metabolism or solubility/dissolution is not rate controlling. Estimating the Graetz number in humans and assuming that Paq is not rate controlling give the following equation for fraction dose absorbed: F = 1 - e-2Pw. The correlation between fraction dose absorbed in humans and Pw 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.