TY - JOUR T1 - Pharmacokinetics of the Rapid-Acting Insulin Analog, Insulin Aspart, in Rats, Dogs, and Pigs, and Pharmacodynamics of Insulin Aspart in Pigs JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 155 LP - 160 VL - 28 IS - 2 AU - Anne Plum AU - Henrik Agersø AU - Lennart Andersen Y1 - 2000/02/01 UR - http://dmd.aspetjournals.org/content/28/2/155.abstract N2 - The objective of this study was to compare the pharmacokinetics and pharmacodynamics of insulin aspart (IA), a rapidly acting insulin analog, with those of human soluble (regular) insulin (HI) in animal models after s.c. and i.v. dosing. Single doses of IA and HI were administered i.v. and s.c. to rats and dogs at three dose levels, and at one dose level to pigs; rats and dogs also underwent repeated s.c. dosing for 1 week. Plasma insulin levels were assessed at predetermined time points after dosing; plasma glucose levels were measured in pigs only. There were no significant pharmacokinetic differences between IA and HI after a single s.c. or i.v. dose in rats or dogs, and no differences were observed after repeated s.c. dosing, implying there was no accumulation. In pigs, there was a strong trend toward more rapid absorption of IA compared with HI after s.c. dosing, whereas there were no differences after i.v. administration. After s.c. dosing in pigs, IA produced significantly lower plasma glucose levels compared with HI during the period 30 to 75 min after dosing (P < .05). In conclusion, IA was more rapidly absorbed than HI after s.c. administration only in the pig; this difference was reflected in earlier and more pronounced effects on plasma glucose levels. The American Society for Pharmacology and Experimental Therapeutics ER -