Pharmacokinetics in Chimpanzees of Recombinant Human Tissue-Type Plasminogen Activator Produced in Mouse C127 and Chinese Hamster Ovary Cells
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概要
- 論文の詳細を見る
Pharmacokinetics of recombinant tissue-type plasminogen activator (rt-PA) produced in mouse C127 cells (t-PA(C127)) and Chinese hamster ovary cells (t-PA(CHO)) was investigated in chimpanzees. rt-PA was administered via a constant rate i.v. infusion for 60 min, and t-PA concentration and activity in plasma were measured during and after infusion. The noncompartmental parameters were calculated according to the moment analysis method, and a population pharmacokinetic analysis was performed to obtain the mean and interindividual variability of the pharmacokinetic parameters. The mean residence time of t-PA(C127) was significantly longer and the total body clearance was significantly less than that of t-PA(CHO). t-PA(C127) has an α-galactosyl moiety in its carbohydrate chains, whereas such a structure is not found in t-PA(CHO). These results demonstrate that two preparations of rt-PA's with different carbohydrate structures show different pharmacokinetics, and suggest that the carbohydrate structure can affect the efficiency of hepatic uptake of t-PA. A possible mechanism is an interaction of t-PA(C127) with the natural anti-α-galactosyl antibody. The anti-α-galactosyl antibody level in plasma decreased in association with the plasma levels of t-PA(C127) but was unaffected by t-PA(CHO) levels.
- 社団法人日本薬学会の論文
- 1990-02-25
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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辻 淳一
東洋紡医薬研
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辻 淳一
東洋紡績 医薬研
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野間 誠司
東洋紡績(株)医薬研究所
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堀 了平
Departments of Pharmacy Kyoto University Hospital, Faculty of Medicine, Kyoto University
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奥村 一夫
Research Institute, Tokobo, Co., Ltd.,
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辻 淳一
Research Institute, Tokobo, Co., Ltd.,
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清水 範英
Research Institute, Tokobo, Co., Ltd.,
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野間 誠司
Research Institute, Tokobo, Co., Ltd.,
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鈴木 潤子
Research Institute, Tokobo, Co., Ltd.,
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LIVINGSTON David
Integrated Genetics, Inc.,
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RICHARDS Susan
Integrated Genetics, Inc.,
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KEYES Lynne
Integrated Genetics, Inc.,
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COUCH Ronald
Primate Research Institute, New Mexico State University
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ERICKSON Mary
Primate Research Institute, New Mexico State University
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Keyes Lynne
Integrated Genetics Inc.
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Erickson Mary
Primate Research Institute New Mexico State University
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Richards Susan
Integrated Genetics Inc.
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奥村 一夫
Research Institute Tokobo Co. Ltd.
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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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鈴木 潤子
Research Institute Tokobo Co. Ltd.
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Couch Ronald
Primate Research Institute New Mexico State University
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堀 了平
近畿大・薬学総合研究所
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Livingston David
Integrated Genetics Inc.
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清水 範英
Research Institute Tokobo Co. Ltd.
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