Prediction of Glycyrrhizin Disposition in Rat and Man by a Physiologically Based Pharmacokinetic Model
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概要
- 論文の詳細を見る
Three physiologically based pharmacokinetic models A-C, incorporating enterohepatic recycling, were developed to predict glycyrrhizin (GLZ) disposition in rat plasma and tissues, and human serum. Model A, which indluded fourteen compartments (artery, vein, tissues except brain, and gut lumen) with the assumption of direct excretion of GLZ from the liver into the gut lumen gave fairly good agreement between the observed and predicted disposition profiles in rat, but was unsuitable in man, where elimination is very rapid. Models B and C for man were obtained by adding a gallbladder compartment (drug storage organ) for the excretion from the liver into the gut lumen and by assuming continuous transfer from the storage compartment or instantaneous amptying from it during meal ingestion as the excretion process from the gallbladder into the gut lumen, respectively. The agreement between the observed and predicted serum concentration time-course profiles was better with model C than model B, especially in the terminal elimination phase, where secondary peaks appeared. However, it was thought that the observed serum disposition can be sufficiently well predicted by model B. In conclusion, prediction in rat was successful in all compartments except the brain, which shows a negligible distribution. Scale-up of the disposition kinetics of GLZ from rat to man was also successful.
- 社団法人日本薬学会の論文
- 1990-01-25
著者
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石田 志朗
Faculty Of Pharmaceutical Sciences Tokushima Bunri University
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平良 全栄
Faculty of Pharmaceutical Sciences, Tokushima Bunri University
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崎谷 陽子
Faculty of Pharmaceutical Sciences, Tokushima Bunri University
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市川 勤
Faculty of Pharmaceutical Sciences, Tokushima Bunri University
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粟津 荘司
Department of Biopharmaceutics, Tokyo College of Pharmacy
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市川 勤
徳島文理大学薬学部医療薬学講座
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市川 勤
東北薬科大学
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粟津 荘司
Department Of Biopharmaceutics Tokyo College Of Pharmacy
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平良 全栄
Faculty Of Pharmaceutical Sciences Tokushima Bunri University
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Sakiya Y
Tokushima Bunri Univ. Tokushima Jpn
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崎谷 陽子
Faculty Of Pharmaceutical Sciences Tokushima Bunri University
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崎谷 陽子
Faculty Of Pharmaceutical Science Tokushima University Of Arts And Science
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