Pharmacokinetics and pharmacodynamics of a premixed formulation of solubleand protamine-retarded insulin aspart

Objective: With the aim to obtain a premixed rapid-acting insulin with a se rum insulin profile more closely resembling the endogenous meal-stimulated serum insulin profiles, a 30/70 (rapid/intermediate-acting) premixed suspen sion of the rapid-acting insulin analogue insulin aspart (BIAsp30) was comp ared with a similar premixed suspension of biphasic human insulin 30/70 (BH I30) after a single subcutaneous injection. Methods: The study had a randomised, double-blind, two-period crossover des ign. Twenty-four healthy male subjects received a single subcutaneous dose of either 0.2 U . kg(-1) bodyweight of BIAsp30 or BHI30 on two study days. Results: BIAsp30 was absorbed faster than BHI30, as reflected in the area u nder the insulin concentration-time curve from 0 to 90 min after dosing [AU C((0-90 min))]. This was significantly larger for BIAsp30 than for BHI30 (1 403 +/- 372 versus 752 +/- 191 mU . l(-1) min(-1) [mean +/- SD]; P < 0.0001 ). Furthermore, the time to maximum serum insulin concentration (t(max)) of BIAsp30 was approximately half the t(max) of BHI30 (60 [45-70] versus 110 [90-180] min [median, interquartile range]; P=0.0001) and the maximum insul in concentration (C-max) was significantly higher for BIAsp30 than for BHI3 0 (23.4 +/- 5.3 versus 15.5 +/- 3.7 mU . l(-1) [mean +/- SD]; P < 0.0001). The serum glucose profiles showed a significantly earlier onset of the gluc ose-lowering effect following BIAsp30 than following BHI30. Conclusions: The improved absorption properties of soluble insulin aspart i n its premixed formulation provide a basis for a more efficient meal-relate d glucose control and immediate pre-meal delivery when compared with a simi lar human premixed insulin in the treatment of diabetes mellitus.