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

Lookup NU author(s): Emeritus Professor Philip Home, Dr Luis Barriocanal


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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 [t(max(ins)) of 52 (23) vs 145 (93) min, P < 0.0001; and C(max(ins)) of 41 (11) vs 18 (4) mU · 1-1, 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 [t(min(PG)) of 94 (45) vs 226 (120) min, P < 0.0001], to a greater extent [C(min(PG)) 2.1 (0.6) vs 1.4 (0.4) mmol · 1-1, 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.

Publication metadata

Author(s): Home PD; Barriocanal L; Lindholm A

Publication type: Article

Publication status: Published

Journal: European Journal of Clinical Pharmacology

Year: 1999

Volume: 55

Issue: 3

Pages: 199-203

Print publication date: 01/05/1999

ISSN (print): 0031-6970

ISSN (electronic): 1432-1041

Publisher: Springer


DOI: 10.1007/s002280050618

PubMed id: 10379635


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