KINETIC STUDY ON DISAPPEARANCE OF γ-BUTYROLACTONE-γ-CARBONYL-L-HISTIDYL-L-PROLINAMIDE (DN-1417) FROM PLASMA USING A RADIOIMMUNOASSAY FOR DN-1417 ISOBUTYLAMIDE
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概要
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Kinetic study of disappearance of γ-butyrolactone-γ-carbonyl-L-histidy-L-prolinamide (DM-1417) from human plasma has been performed by a sensitive and specific radioimmunoassay (RIA) using antiserum against DN-1417 isobutylamide. Antibody against N-[2-hydroxy-4-(isobutylcarbamoyl)butyryl]-L-histidy-L-prolinamide (DN-isobutylamide) did not cross-react with any other TRH-related peptides tested. DN-isobutylamide was radioiodinated with ^<125>I by the chloramine T method and the product had a specific activity of about 160μCi/μg. The sensitivity of the RIA was 50pg per tube, and the intra- and inter-assay coefficients of variation at concentrations of 1-10ng/ml were 7.0-11.6%. DN-1417 in the plasma was converted to a stable form, DN-isobutylamide, by incubation with isopropanol-isobutylamine at room temperature for 2h. DN-Isobutylamide was separated from 2-hydroxy-4-carboxybutyryl-L-histidyl-L-prolinamide (DN-COOH) using a SEP-PAK^<TM> C_<18> cartridge before RIA. The recovery of DN-isobutylamide from plasma was 86.2-98.2%. The half-life, volume of distribution and plasma clearance rate of DN-1417 examined in 6 normal male volunteers by intravenous injection of 500μg DN-1417 citrate were 11.5±5.6min in the first phase and 89.5±33.5min in the second phase, 25.3±10.0 liters and 745.8±278.6 1/d, respectively. These results indicate that RIA of DN-isobutylamide is useful for analysing DN-1417 metabolism in humans.
- 公益社団法人日本薬学会の論文
著者
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SAITO SHIRO
First Department of Internal Medicine,School of Medicine,The University of Tokuhsima
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Shiota Kunio
Central Research Division Takeda Chemical Industries Ltd.
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NAKAYAMA RYO
Central Research Division, Takeda Chemical Industries, Ltd.
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Nakayama Ryo
Central Research Division Takeda Chemical Industries Ltd.
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Miyake Akio
Central Research Division Takeda Chemical Industries Ltd.
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OSHIMA ICHIYO
Department of Laboratory Medicine, Tokushima University School of Medicine
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OKA YOSHIKAZU
Central Research Division, Takeda Chemical Industries, Ltd.
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Oshima Ichiyo
Department Of Laboratory Medicine Tokushima University School Of Medicine
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Saito Shiro
First Department Of Internal Medicine Tokushima University School Of Medicine
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Oka Yoshikazu
Central Research Division Takeda Chemical Industries Ltd.
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Saito Shiro
First Department Of Internal Medicine School Of Medicine School Of Medicine The University Of Tokush
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OSHIMA ICHIYO
Department of Clinical Laboratory, Tokushima University Hospital, Faculty of Medicine Tokushima University
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