Pulmonary and Hepatic Disposition of Hippuryl-L-Histidyl-L-Leucine
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概要
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The pulmonary and hepatic clearances of the synthesized angiotensin converting enzyme (ACE) substrate, hippuryl-L-histidyl-L-leucine (HHL) were evaluated by applying the multiple sites of input method and the recirculation pharmacokinetic model. Rats received a constant rate infusion via the carotid artery, jugular vein or portal vein in the absence or presence of the ACE inhibitor, captopril. Blood samples were collected from the femoral artery. The organ extraction ratio was calculated from the steady-state plasma concentrations and the mean organ transit time was computed as the difference in the mean residence times for various administration routes. Pronounced elimination in the lung and liver was observed in the absence of captopril. Pulmonary metabolism was completely depressed in the presence of captopril while the hepatic elimination was little affected. This suggests that the pulmonary elimination was entirely ascribed to ACE while there exists an alternative elimination process in the liver. The mean cardiopulmonary transit time was very short, indicating the pulmonary elimination of HHL may take place on the surface of the vascular endothelium. The evaluation of the pulmonary elimination of HHL described in this paper indicates a simple in vivo method for assessing the pharmacological effect of ACE inhibitors. The present pharmacokinetic approach will be useful for the quantification of drug disposition in individual organs in vivo.
- 社団法人日本薬学会の論文
- 1991-03-25
著者
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谷川原 祐介
Department Of Pharmacy Kyoto University Hospital Faculty Of Medicine Kyoto University
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奥村 勝彦
Department of Hospital Pharmacy, School of Medicine, Kobe University
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堀 了平
Departments of Pharmacy Kyoto University Hospital, Faculty of Medicine, Kyoto University
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何 艶玲
Department Of Pharmacy Kyoto University Hospital
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堀 了平
Department Of Pharmacy Kyoto University Hospital
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堀 了平
Pharmaceutical Research And Technology Institute Kinki University
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Hori R
Kinki Univ. Higashi‐osaka Jpn
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堀 了平
近畿大・薬学総合研究所
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