European Journal of Clinical Pharmacology

, Volume 55, Issue 3, pp 199–203

Comparative pharmacokinetics and pharmacodynamics of the novel rapid-acting insulin analogue, insulin aspart, in healthy volunteers

  • P. D. Home
  • L. Barriocanal
  • A. Lindholm
PHARMACODYNAMICS

DOI: 10.1007/s002280050618

Cite this article as:
Home, P., Barriocanal, L. & Lindholm, A. E J Clin Pharmacol (1999) 55: 199. doi:10.1007/s002280050618

Abstract

Objective: The pharmacokinetics of a new insulin analogue, insulin aspart, were compared with unmodified human insulin in a double-blind crossover study of 25 fasting healthy men following a single subcutaneous dose.

Methods: Either insulin aspart or human insulin, 0.1 U · kg-body-weight−1, was injected subcutaneously and followed by determination of 8-h profiles of serum insulin and plasma glucose concentrations.

Results: The absorption of insulin aspart was, on average, more than twice as fast and reached levels more than twice as high compared with human insulin [tmax(ins) of 52 (23) vs 145 (93) min, P < 0.0001; and Cmax(ins) of 41 (11) vs 18 (4) mU · l−1, P < 0.0001; mean with (SD)]. However, total bioavailability did not differ between the insulins, and thus the mean residence time was significantly shorter for insulin aspart [MRT(ins) of 149 (26) vs 217 (30) min, P < 0.0001]. Plasma glucose (PG) fell more than twice as rapidly [tmin(PG) of 94 (45) vs 226 (120) min, P < 0.0001], to a greater extent [Cmin(PG) 2.1 (0.6) vs 1.4 (0.4) mmol · l−1, P < 0.0001], and for a shorter duration with insulin aspart than with human insulin.

Conclusion: With improved subcutaneous absorption characteristics, the insulin aspart concentration–time profile resembles physiological meal-stimulated insulin release more closely than that of unmodified human insulin. This significantly alters the pharmacodynamic response in an advantageous manner in the meal-related treatment of diabetes mellitus.

Key words Insulin aspart Insulin absorption Rapid-acting insulin analogue 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • P. D. Home
    • 1
  • L. Barriocanal
    • 1
  • A. Lindholm
    • 2
  1. 1.Human Diabetes and Metabolism Research Centre, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK e-mail: Philip.Home@newcastle.ac.uk Tel.: +44-191-222-7019; Fax: +44-191-222-0723GB
  2. 2.Novo Nordisk A/S, Bagsvaerd, DenmarkDK