THE INTESTINAL DIALYSIS OF INTRAVENOUSLY ADMINISTERED PHENYTOIN BY ORAL ACTIVATED CHARCOAL IN RATS
スポンサーリンク
概要
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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.
- 公益社団法人日本薬学会の論文
著者
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Nakano Masahiro
Department Of Biologicalsciences Teikyo University Of Science And Technology
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Arimori Kazuhiko
Department Of Pharmacy Kumamoto University Hospital
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Nakano Masahiro
Deparment Of Physics Kyushu University
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Arimori Kazuhiko
Department Of Pharmacy Faculty Of Medicine University Of Miyazaki
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