ラットにおける塩酸バンコマイシンの難吸収に関与する要因の検討

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  • Factors Involved in Poor Absorption of Vancomycin in Rats

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<p>It is well known that vancomycin (VCM), a glycopeptide antibiotic, is very poorly absorbed from the gastrointestinal tract after oral administration. In this study, we examined the factors involved in the poor absorption of VCM in the rat intestine. The disappearance of VCM from in situ intestinal loop was greater than that of phenol red, a poorly absorbable compound. However, VCM was slightly detected in the plasma at the end of the absorption experiment. It was shown that this glycopeptide was very stable in the supernatant of intestinal mucosal homogenate and that its binding to gastric mucin was not so remarkable compared with chlorpromazine. When the in vitro permeation behavior of VCM across rat intestine was evaluated in the Ussing chamber system, VCM exhibited a secretoryoriented manner in both the jejunum and ileum. The ratio of serosal-to-mucosal/mucosal-to-serosal permeation was 2.40 in the jejunum and 3.15 in the ileum. When d-glucose was replaced with 3-O-methyl-d-glucose in the experimental medium, the ratio in the ileum was modified to 1.62. Verapamil and cyclosporine A, known P-glycoprotein modulators, significantly enhanced the mucosal-to-serosal permeation of VCM, while tetraethylammonium and guanidine had no effect on it. It was suggested that intestinal P-glycoprotein might be involved in the poor absorption of VCM from rat small intestine as a potent barrier.</p>

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  • 薬剤学

    薬剤学 59 (3), 103-112, 1999

    公益社団法人 日本薬剤学会

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