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标题：ABSORPTION OF γ-BUTYROLACTONE-γ-CARBONYL-L-HISTIDYL-L-PROLINAMIDE CITRATE (DN-1417), AN ANALOG OF THY-ROTROPIN-RELEASING HORMONE, IN RATS AND DOGS
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作者：SHIGEHARU YOKOHAMA ; TOSHIO YOSHIOKA ; NOBUYUKI KITAMORI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1984
卷号：7
期号：8
页码：527-535
DOI：10.1248/bpb1978.7.527
出版社：The Pharmaceutical Society of Japan
摘要：Plasma levels of γ-butyrolactone-γ-carbonyl-L-histidyl-L-prolinamide citrate (DN-1417), an analog of thyrotropin-releasing hormone, were determined by a radio-immunoassay after oral or intravenous administration in rats and dogs. A pharmacokinetic analysis after intravenous injection revealed biphasic elimination of the plasma concentration following a two compartment open model with half lives in α-phase of 2.0 min and β-phase of 19.2 min in rats, and half lives in a-phase of 4.0 min and β-phase of 33.0 min in dogs. Absolute bioavailabilities when administered orally the solution of DN-1417 after 24 h fasting in rats and dogs were 1 and 10%, respectively. The bioavailability was observed to be unchanged at the dose up to 500 mg/kg in rats and at the dose up to 100 mg/dog in dogs. Thus, the absorption of DN-1417 in rats and dogs was proportional to the dose. On the other hand, the absolute bioavailabilities after meal in dogs were 7.9% at the dose of 20 mg/dog and 7.2% at the dose of 2 mg/dog, whereas in the 24 h fasting condition they were 15.7 and 12.0%, respectively, showing the decrease in absorption with food ingestion. These phenomena are somewhat different from the absorption of thyrotropin-releasing hormone.
关键词：pharmacokinetic parameter