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 · 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.