Effect of protein on the absorption of phenytoin through everted gut preparations.

The transfer of phenytoin across everted gut membrane has been measured both from solutions and from media where the drug is dissolving at different pH. Introduction of protein into the mucosal medium caused varying effects. Protein binding in the mucosal solution causes a decrease in the apparent transfer rate. However, in accord with previous findings, at pH 4 both the solubility and dissolution rate of phenytoin increase in the presence of protein, and this can lead to increased transfer rates. Effects such as these may account for the effect of food on phenytoin bioavailability.