Pharmacokinetics of the rapid-acting insulin analog, insulin aspart, in rats, dogs, and pigs, and pharmacodynamics of insulin aspart in pigs

The objective of this study was to compare the pharmacokinetics and pharmac odynamics of insulin aspart (IA), a rapidly acting insulin analog, with tho se 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 r ats 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 lev els were measured in pigs only. There were no significant pharmacokinetic d ifferences between IA and HI after a single s.c. or i.v. dose in rats or do gs, and no differences were observed after repeated s.c. dosing, implying t here was no accumulation. In pigs, there was a strong trend toward more rap id 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 pro duced significantly lower plasma glucose levels compared with HI during the period 30 to 75 min after dosing (P < .05). In conclusion, IA was more rap idly absorbed than HI after s.c. administration only in the pig; this diffe rence was reflected in earlier and more pronounced effects on plasma glucos e levels.