猪体内羧酰胺化和甘氨酸延伸胃泌素的药代动力学及器官代谢

Pharmacokinetics and organ metabolism of carboxyamidated and glycine-extended gastrins in pigs.

作者信息

Hansen C P, Stadil F, Yucun L, Rehfeld J F

机构信息

Department of Gastrointestinal Surgery, Rigshospitalet, University of Copenhagen, Denmark.

出版信息

Am J Physiol. 1996 Jul;271(1 Pt 1):G156-63. doi: 10.1152/ajpgi.1996.271.1.G156.

DOI:10.1152/ajpgi.1996.271.1.G156

PMID:8760119

Abstract

The elimination of carboxyamidated gastrin-17 and its glycine-extended precursor was studied in anesthetized pigs during constant-rate infusion. Extraction of amidated gastrin-17 was recorded in the hindlimb (42%), kidney (40%), head (32%, P < 0.001), and the gut (13%, P < 0.01). Elimination was not recorded in the liver, lungs, or heart. Extraction of glycine-extended gastrin-17 was measured in the kidney (36%), hindlimb (31%, P < 0.001), head (26%), and the gut (16%, P < 0.01), but not in the liver or the lungs. Glycine-extended gastrin-17 was not processed to amidated gastrin during infusion. The half-life, metabolic clearance rate, and apparent volume of distribution for amidated gastrin-17 were 3.5 +/- 0.4 min, 15.5 +/- 1.1 ml.kg-1.min-1, and 76.5 +/- 9.9 ml/kg, respectively, and for glycine-extended gastrin-17 were 4.3 +/- 0.6 min, 17.4 +/- 0.9 ml.kg-1.min-1, and 104.7 +/- 11.9 ml/kg, respectively. We conclude that extraction of amidated and glycine-extended gastrin-17 varies in the vascular beds, with elimination mainly confined to nonorgan tissues and the kidneys.

摘要

在麻醉猪恒速输注过程中，对羧基酰胺化胃泌素-17及其甘氨酸延伸前体的清除情况进行了研究。在猪的后肢（42%）、肾脏（40%）、头部（32%，P<0.001）和肠道（13%，P<0.01）记录到了酰胺化胃泌素-17的提取。在肝脏、肺或心脏中未记录到清除情况。在肾脏（36%）、后肢（31%，P<0.001）、头部（26%）和肠道（16%，P<0.01）测量到了甘氨酸延伸胃泌素-17的提取，但在肝脏或肺中未检测到。在输注过程中，甘氨酸延伸胃泌素-17未加工成酰胺化胃泌素。酰胺化胃泌素-17的半衰期、代谢清除率和表观分布容积分别为3.5±0.4分钟、15.5±1.1毫升·千克⁻¹·分钟⁻¹和76.5±9.9毫升/千克，甘氨酸延伸胃泌素-17的半衰期、代谢清除率和表观分布容积分别为4.3±0.6分钟、17.4±0.9毫升·千克⁻¹·分钟⁻¹和104.7±11.9毫升/千克。我们得出结论，酰胺化和甘氨酸延伸胃泌素-17在血管床中的提取情况不同，清除主要局限于非器官组织和肾脏。