首页 | 本学科首页   官方微博 | 高级检索  
     


Insulin pharmacokinetics following continuous infusion and bolus injection of regular porcine and human insulin in healthy man
Authors:Werner K. Waldhäusl  Paul R. Bratusch-Marrain  Heinrich Vierhapper  Peter Nowotny
Affiliation:Division of Clinical Endocrinology and Diabetes Mellitus, I. Medizinische Universitätsklinik, Vienna, Austria.
Abstract:To determine the pharmacokinetics of insulin administered by intravenous (IV) and subcutaneous (SC) pump treatment as well as by the conventional subcutaneous route, six insulin preparations of either porcine or human amino acid sequence were investigated intraindividually following IV or SC insulin infusion at two different rates (Study I) and three preparations were investigated after SC bolus injection (Study II) in healthy men. Insulin release was suppressed in Study I by IV administration of somatostatin (500 μg/hr) to avoid interference by endogenous insulin with the measurement of exogenous insulin. Hypoglycemia was prevented by IV administration of glucose. The data obtained demonstrated (1) greater serum concentrations of immunoreactive insulin (IRI) during continuous IV insulin infusion (141 ± 10 (SEM) pmole/liter) than during SC insulin infusion (54 ± 3 pmole/liter; P < 0.0005) (0.8 U/hr); (2) return of serum IRI to baseline values following a 17-minute square wave insulin infusion (12.8 U/hr; time: 0 to 17 minutes) within 40 minutes after IV insulin infusion but not before 180 minutes after the end of SC insulin infusion; (3) peak serum IRI at 60 to 90 minutes after conventional SC insulin injection returning to baseline values at 300 minutes; and (4) identity of the pharmacokinetics of pumped human and porcine insulin within a given group as well as of the accompanying metabolic dynamics of blood glucose and nonesterified fatty acids, but heterogeneity of serum insulin after its SC bolus injection. We conclude that (1) the pharmacokinetic behavior of regular insulin depends primarily on its route of administration; (2) continuous IV infusion of an insulin dose causes significantly higher serum insulin levels than the SC administration of the identical insulin dose, and (3) hyperinsulinemia caused by a square wave insulin infusion (12.8 U/hr; time: 0 to 17 minutes) requires more than four times longer to return to baseline levels following SC administration than after IV administration of the insulin. These differences in the pharmacokinetic behavior of insulin cause a reduced bioavailability of SC administered insulin and have to be taken into account when instituting insulin treatment by various routes.
Keywords:Address reprint requests to Werner K. Waldhäusl   MD   Division of Clinical Endocrinology and Diabetes Mellitus   I. Medizinische Universitätsklinik   Lazarettgasse 14   A 1090 Wien   Austria.
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号