文章基本信息

标题：INTESTINAL ABSORPTION MECHANISMS OF γ-BUTYROLACTONE-γ-CARBONYL-L-HISTIDYL-L-PROLINAMIDE CITRATE (DN-1417) AND THYROTROPIN-RELEASING HORMONE (TRH)
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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：1985
卷号：8
期号：4
页码：278-285
DOI：10.1248/bpb1978.8.278
出版社：The Pharmaceutical Society of Japan
摘要：The absorption mechanisms of γ-butyrolactone-γ-carbonyl-L-histidyl-L-prolinamide citrate (DN-1417) and thyrotropin-releasing hormone (TRH) were studied in the rat. In situ absorption experiments were carried out by radioimmunoassay, and experiments using everted sacs of small intestine were by radioactivity measurements with ¹⁴C-labeled DN-1417 or ³H-labeled TRH in the low concentration range of drug and by a high pressure liquid chromatography in the rather high concentration range of drug. The site specificity of absorption in the small intestine of rats could not be found with DN-1417 whereas TRH-T was absorbed from only the upper part of small intestine. Dose-proportional absorption of of DN-1417 was observed in experiments of in situ as well as in vitro. Dose-proportional transfer of DN-1417 through the everted small intestine was also found within the concentration range from 120 ng/ml to 27 mg/ml, whereas the transfer ratio of TRH decreased with increase in the concentration of TRH. DN-1417 transfer from mucosal to serosal fluid was not inhibited by the replacement of medium Na ions by K ions, pretreatment of intestinal mucosa with HgCl₂, the existence of an oligopeptide, or the existence of β-lactam antibiotics which had been reported to be absorbed by active transport or carrier-mediated transport systems. While, TRH transfer was inhibited by the replacement of medium Na ions by K ions, pretreatment of intestinal mucosa with HgCl₂, the existence of an oligopeptide, and the existence of β-lactam antibiotics. From these results, it was concluded that DN-1417 transfer through the small intestine was mainly due to the simple diffusion, and the contribution of the carrier-mediated transport to TRH transfer through the small intestine was not disregarded
关键词：β-Lactam antibiotic