Pharmacokinetics and pharmacodynamics of a premixed formulation of soluble and protamine-retarded insulin aspart.
OBJECTIVE
With the aim to obtain a premixed rapid-acting insulin with a serum insulin profile more closely resembling the endogenous meal-stimulated serum insulin profiles, a 30/70 (rapid/intermediate-acting) premixed suspension of the rapid-acting insulin analogue insulin aspart (BIAsp30) was compared with a similar premixed suspension of biphasic human insulin 30/70 (BHI30) after a single subcutaneous injection.


METHODS
The study had a randomised, double-blind, two-period crossover design. Twenty-four healthy male subjects received a single subcutaneous dose of either 0.2 U x kg(-1) bodyweight of BIAsp30 or BHI30 on two study days.


RESULTS
BIAsp30 was absorbed faster than BHI30, as reflected in the area under the insulin concentration-time curve from 0 to 90 min after dosing [AUC(0-90 min)]. This was significantly larger for BIAsp30 than for BHI30 (1403 +/- 372 versus 752 +/- 191 mU x l(-1) x min(-1) [mean +/- SD]; P < 0.0001). Furthermore, the time to maximum serum insulin concentration (tmax) of BIAsp30 was approximately half the tmax of BHI30 (60 [45-70] versus 110 [90-180] min [median, interquartile range]; P=0.0001) and the maximum insulin concentration (Cmax) was significantly higher for BIAsp30 than for BHI30 (23.4 +/- 5.3 versus 15.5 +/- 3.7 mU x l(-1) [mean +/- SD]; P < 0.0001). The serum glucose profiles showed a significantly earlier onset of the glucose-lowering effect following BIAsp30 than following BHI30.


CONCLUSIONS
The improved absorption properties of soluble insulin aspart in its premixed formulation provide a basis for a more efficient meal-related glucose control and immediate pre-meal delivery when compared with a similar human premixed insulin in the treatment of diabetes mellitus.
Jacobsen
L V
LV
Clinical Drug Development, Novo Nordisk A/S, Bagsvaerd, Denmark.
Søgaard
B
B
Riis
A
A
D000042:Absorption; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D007279:Injections, Subcutaneous; D049528:Insulin, Long-Acting / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting