Effect of Triazole Antifungal Agents on the Drug Secretion Process in Rat Small Intestine: Contribution of P‐glycoprotein

Abstract

The effect of triazole antifungal agents on the drug secretion process from the serosal to the mucosal side in small intestine was studied using rat everted intestinal sacs. Rhodamine 123 was used as a model drug mediated by P-glycoprotein. The effect of inhibitors, verapamil and triazole antifungal agents was investigated by measuring the efflux of rhodamine 123. Efflux was significantly reduced by the addition of verapamil. Fluconazole had no effect on the efflux of rhodamine 123, while the efflux of rhodamine 123 was significantly reduced by oral administration of itraconazole. These results suggest that inhibition of drug secretion by P-glycoprotein in intestine may be involved in the interaction between various drugs and itraconazole.