Tissue Distribution and Metabolism of Drugs. I. Quantitative Investigation on Renal Handling of Phenolsulfonphthalein and Sulfonamides in Rabbits
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概要
- 論文の詳細を見る
In order to analyze the renal handling of drugs under more suitable conditions to enable clinical application, renal clearance method based on computer analysis after administering a single dose of a drug was developed in rabbits. Phenolsulfonphthalein, sulfamethoxazole, sulfanilamide, and sulfamethizole which present characteristically different renal handling were studied, and it had been demonstrated that the results of analysis of our proposed model agreed well with the data obtained by combining the clearance experiments of constant-infusion technique with inhibitory experiments using iodopyracet. The order of reabsorption fraction was similar to that of the partition coefficient of these drugs. The renal tubular reabsorption of these drugs was dependent upon nonionic diffusion which could be explained by lipoid solubility of the drug, while tubular secretion could be explained by active transport that conformed to the Michaelis-Menten equation. Further, it was presumed that the tubular secretion of these drugs was dependent upon the unbound drug concentration in plasma. From these results, a comprehensive scheme which elucidated the renal handling of these four drugs was proposed. In this method as neither constant infusion nor massive dose loading of secretion inhibitors were used, the experiment was conducted under comparatively less harsh conditions than the standard renal clearance and inhibitory experiments. Thus, it is felt that this method can be safely applied to humans.
- 公益社団法人日本薬学会の論文
- 1978-03-25
著者
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堀 了平
京都大学医学部附属病院薬剤部
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堀 了平
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine
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砂屋敷 幸作
Institute of Pharmaceutical Sciences, Hiroshima University, School of Medicine
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神谷 晃
Institute of Pharmaceutical Sciences, Hiroshima University, School of Medicine
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砂屋敷 幸作
Institute Of Pharmaceutical Sciences Hiroshima University School Of Medicine
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