キニジンのラット小腸吸収および血中濃度パターンに及ぼす酸性多糖体の影響と分子間相互作用から見たその機構

概要

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Examination was made on the effect of acid polysaccharides on the intestinal absorption of quinidine in rats, and also on the intermolecular interaction between quinidine and polysaccharides. The absorption in situ of quinidine was inhibited markedly by dextran sulfate (Na salt). Sodium carboxymethylcellulose and sodium alginate showed a weaker inhibitory effect. The inhibitory effect of dextran sulfate on the absorption was well reflected on the blood level patterns of quinidine administered into the small intestine by the loop method ; the time of the maximum blood level was delayed in the presence of dextran sulfate, and after that time, the blood level of quinidine became higher than that in the absence of the polysaccharide. The degree of binding of quinidine and polysaccharides was quantified by the use of ultrafiltration and fluorescence analysis. A parallel relationship was established between the order of inhibitory effect of polysaccharides on the intestinal absorption of quinidine and the order of binding ratios of the quinidine-polysaccharide systems. Based on the results of analysis of the mode of binding, it was presumed that, in the physiological pH region, dissociation of the quinuclidine ring of quinidine played an important role in the ionic binding of quinidine and dextran sulfate.
公益社団法人日本薬学会の論文
1977-12-25