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Estimating Human Oral Fraction Dose Absorbed: A Correlation Using Rat Intestinal Membrane Permeability for Passive and Carrier-Mediated Compounds

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Abstract

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 gives the following equation for fraction dose absorbed: F = 1− e −2 P*w. The correlation between fraction dose absorbed in humans and P w * determined from steady-state 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.

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Amidon, G.L., Sinko, P.J. & Fleisher, D. Estimating Human Oral Fraction Dose Absorbed: A Correlation Using Rat Intestinal Membrane Permeability for Passive and Carrier-Mediated Compounds. Pharm Res 5, 651–654 (1988). https://doi.org/10.1023/A:1015927004752

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  • DOI: https://doi.org/10.1023/A:1015927004752

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