Comparative pharmacokinetics and pharmacodynamics of the novel rapid-acting insulin analogue, insulin aspart, in healthy volunteers.
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 x 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 x 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 x l(-1), P < 0.0001], and for a shorter duration with insulin aspart than with human insulin.


CONCLUSIONS
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.
Home
P D
PD
Human Diabetes and Metabolism Research Centre, The Medical School, Newcastle upon Tyne, UK. Philip.Home@newcastle.ac.uk
Barriocanal
L
L
Lindholm
A
A
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D007328:Insulin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D061267:Insulin Aspart; D008297:Male; D008875:Middle Aged
D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart