Effect of Cholestyramine on the Pharmacokinetics and Pharmacodynamics of Bezafibrate in Rats

概要

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The interaction between bezafibrate (BF) and cholestyramine (CT), an anionic exchange resin, was evaluated both in vitro and in vivo. In an in vitro study, the incubation of 100 or 1000 μg/ml of BF solution with 200 mg of CT at various pH (2.0, 5.0 and 7.0) solutions was performed at 37℃ for 10 min in order to evaluate the binding ability of BF to CT. After incubation, 100 μg/ml of BF bound to CT by 85.41, 89.40 and 92.14% at pH 2, 5 and 7, respectively, and 1000 pglml of BF bound to CT by 66.28 and 69.02%, at pH 5 and 7, respectively. Next, the effect of CT on the pharmacokinetics and pharmacodynamics of BF was examined in experimentally induced hypercholesterolemic rats. When BF (50 mg/kg/day p. o.) and CT (600 mg/kg/day p.o.) were continuously administered to rats once a day for 7 days, CT caused a significant reduction in the cholesterol-lowering effect of BF in accordance with a significant decrease in the plasma level of BF, compared with the administration of BF alone. The decreased plasma BF Ievel closely reflected the cholesterol-Iowering effect of BF. Even when CT was given 3h after BF, the pharrnacokinetics and pharrnacodynamics of BF were not sufficient to achieve a full recovery of the BF Ievel. The present observations thus suggest that CT should be used with extreme caution in patients receiving BF.
日本医療薬学会の論文
1997-04-10