Cathapermal S S, Foegh M L, Rau C S, Ramwell P W
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007.
Drug Metab Dispos. 1991 Jul-Aug;19(4):735-9.
The disposition and tissue distribution of angiopeptin, a long-acting octapeptide analogue of somatostatin, were studied in rats following single iv and sc administration of the drug. Similar plasma levels and excretion values of angiopeptin were observed by using radioimmunoassay and radiolabeling techniques. Angiopeptin was absorbed fairly rapidly, with a mean peak plasma level of 25 +/- 4.1 ng/ml at 10-15 min after administration. The kinetics of angiopeptin following sc administration closely resembled those following iv administration due to rapid absorption. The pharmacokinetics of angiopeptin can be described by a two-compartment model. The plasma half-life of the drug ranged from 2.6-2.9 hr when administered sc and 1.98-2.5 hr when given iv. Distribution of angiopeptin was rapid, with the highest concentration appearing in the liver. Half-lives in the liver and bile were short. Most of the drug was excreted in the feces via the bile, while approximately 10% was excreted in the urine. Angiopeptin was also found to be secreted in the saliva. TLC and HPLC of blood, urine, feces, and bile samples did not reveal the presence of any metabolites. In conclusion, the in vivo fate of angiopeptin is characterized by little or no hepatic metabolism and rapid biliary excretion.
在大鼠单次静脉注射和皮下注射生长抑素长效八肽类似物血管肽素后，对其处置和组织分布进行了研究。通过放射免疫分析和放射性标记技术观察到血管肽素具有相似的血浆水平和排泄值。血管肽素吸收相当迅速，给药后10 - 15分钟血浆平均峰值水平为25±4.1 ng/ml。由于吸收迅速，皮下注射后血管肽素的动力学与静脉注射后极为相似。血管肽素的药代动力学可用二室模型描述。皮下给药时药物的血浆半衰期为2.6 - 2.9小时，静脉注射时为1.98 - 2.5小时。血管肽素分布迅速，肝脏中浓度最高。在肝脏和胆汁中的半衰期较短。大部分药物通过胆汁经粪便排泄，约10%经尿液排泄。还发现血管肽素分泌于唾液中。血液、尿液、粪便和胆汁样本的薄层层析和高效液相色谱分析未显示存在任何代谢物。总之，血管肽素的体内转归特点是肝脏代谢极少或无代谢，且经胆汁快速排泄。
