消化管内細菌によるクロナゼパムの還元

概要

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The possibility of metabolism of clonazepam with fresh stool was investigated because a low correlation had been observed between a clonazepam dose and its serum concentrations, and very low bioavailability had been observed when a single dose of a nonmicronized drug in a gelatin capsule was administered orally. After combination of clonazepam with sterilized broth (pH 7.2), 1% (pH 5.9) or 8% (pH 5.5) sterilized stool culture without further anaerobic precautions, the drug did not degrade in the incubation mixture. This indicates that the drug did not react with the components of broth and stool cultures, and was stable at these pH values. On the other hand, after combination of the drug with 1% or 8% human faecal contents in a broth, the drug disappeared rapidly in the incubation mixture in proportion to stool concentrations. The metabolite was identified to be 7-aminoclonazepam by high performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). The degradation of clonazepam and the appearance of a metabolite, 7-aminoclonazepam were followed by HPLC and TLC.
公益社団法人日本薬学会の論文
1985-10-25