The intestinal dialysis of intravenously administered phenytoin by oral activated charcoal in rats.

Abstract

The effect of oral administration of activated charcoal on total body clearance of phenytoin following intravenous administration was studied in rats. In situ single-pass perfusion study showed that phenytoin was exsorbed into the small intestinal lumen. The exsorption of the drug from blood into the intestinal lumen was increased in a dose-dependent manner. The exsorption rate of the drug at the dose of 10 mg/kg was 1.1% in 120 min, while that at 50 mg/kg was 2.5% in 120 min. The excretion of the conjugate of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) into the bile was greater than phenytoin and unconjugated p-HPPH and the total percentage of excretion of p-HPPH was significantly decreased by increasing the dose. Oral activated charcoal had little effect on the serum phenytoin levels after the 10 mg/kg dose. On the other hand, charcoal reduced the serum phenytoin levels after the 50 mg/kg dose as compared with the corresponding controls. Oral administration of activated charcoal decreased the serum half-life to 77% and the area under the serum concentration-time curve to 75% after the 50 mg/kg dose of phenytoin. The apparent volume of distribution was not significantly different between rats with activated charcoal treatment and rats without charcoal treatment. Based on these results, a mechanism of the enhanced clearance of phenytoin at a high dose (50 mg/kg) may be due to the adsorption of the drug and its metabolites transported into the gastrointestinal tract by the charcoal.