Studies of Absorption Promoters for Rectal Delivery Preparations. II. A Possible Mechanism of Promoting Efficacy of Enamine Derivatives in Rectal Absorption

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The effect of calcium ions on the promoting efficacies of enamine derivatives for rectal absorption of water-soluble β-lactam antibiotics was investigated in vivo and in vitro. Ethyl acetoacetate enamine derivatives of phenylglycine and ampicillin, which are membrane-permeable and have calcium binding ability, enhanced the rectal absorption of water-soluble β-lactam antibiotics. The promoting efficacy of the enamine derivative for ampicillin was larger than that of water-soluble chelating agents such as EDTA 2Na and trisodium citrate. The blood level-time profile of ampicillin after rectal administration of the enamine derivative of ampicillin was not influenced by the presence of calcium chloride in the suppository. However, the promoting potency of the enamine derivative for rectal absorption of co-existing ampicillin decreased in the presence of calcium chloride in the suppository. The enamine derivative of phenylglycine-Ca^<2+> complex was proved to be permeable through the rat rectal sac in vitro, although the complex had no promoting potency for the permeation of ampicillin through the rectal sac. The loss of absorption promoting potency upon calcium complex formation by the enamine was also found in in vivo experiments. This finding suggests that the role of enamine derivatives as rectal absorption promoters for water-soluble antibiotics is based upon their calcium binding ability.
社団法人日本薬学会の論文
1982-02-25