Abstract
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.
Footnotes
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Send reprint requests to: Anne Plum, Pharmacokinetics Department, Novo Nordisk A/S, Novo Nordisk Park 2760 Måløv, Denmark. E-mail: anp{at}novo.dk
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These studies were supported by Novo Nordisk A/S.
- Abbreviations used are::
- IA
- insulin aspart
- HI
- human soluble (regular) insulin
- AUC
- area under the concentration-time curve
- Received March 12, 1999.
- Accepted August 12, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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