Sodium Valproate, PhenobarbitalとCarvedilolのラット血漿中濃度に及ぼすColestimideの影響

Abstract

Colestimide is a new anion exchange resin synthesized from 2-metyl imidazole and epichlorohydrin, and shows a specific affinity to bile acids among physiological anions. The drug interaction of colestimide with sodium valproate, phenobarbital and carvedilol in the gastrointestinal absorption in male rats was examined.The plasma valproate concentrations in the treatment with colestimide were significantly lower than those in the control at 15 min-1 hr, and the drug pharmacokinetic parameters, Cmax and AUC0-∞ were 40 and 25% decreased after oral administration of 100 mg/kg sodium valproate with 1.05 g/kg colestimide. The plasma phenobarbital concentrations were significantly lower than the control at 30 min-1 hr, and tmax was 3.0 times delayed after oral administration of 80 mg/kg phenobarbital with 1.05 g/kg colestimide. On the other hand, the administration of 20 mg/kg carvedilol with 1.05 g/kg colemide did not change the time dependent profiles of the plasma concentration and pharmacokinetic parameters of carvedilol.These result suggested that the absorption of sodium valproate was decreased and the absorption of phenobarbital was delayed by the coadministrated colestimide, but no significant effect on the bioavailability of carvedilol was observed.