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Influence of bile on the gastrointestinal absorption of phenytoin in rats.

The influence of endogeneous bile on the gastrointestinal absorption of phenytoin (DPH) was studied in rats after oral administration of DPH as an aqueous or oil suspension. A bile salt such as sodium taurocholate considerably enhanced DPH dissolution and solubility. The bioavailability of DPH from aqueous suspension was significantly lower in bile duct-ligated rats than in control or sham-operated animals. When DPH was administered to bile duct-ligated rats as a sesame oil suspension, its maximum blood concentration was significantly lower than that in sham-operated rats. These results suggest that endogenous bile plays an important role in the dissolution of DPH and the emulsification or dispersion of oil in the gastrointestinal tract. After laparotomy, DPH administered with vehicles of high viscosity, such as sesame oil, showed significantly delayed absorption but increased bioavailability.