NovoSol Basal: pharmacokinetics of a novel soluble long acting insulin analogue.
OBJECTIVE
To determine the courses of absorption and the interindividual and intraindividual variations in absorption of iodine-125 labelled Ultratard HM and NovoSol Basal injected subcutaneously.


METHODS
Open randomised crossover study. Each patient was tested during two study periods of five days each, during which he or she received a subcutaneous injection of either 125I-NovoSol Basal or 125I-Ultratard HM on four consecutive days. The aim was to detect a reduction in intraindividual standard deviation by a factor of two with a probability 0.95, taking 0.05 as the level of significance. This required 24 degrees of freedom and led to the choice of four courses in each of eight patients.


METHODS
Referrals to the diabetes research centre in Hvidøre, Copenhagen.


METHODS
Eight insulin dependent (type I) diabetics with low or undetectable C peptide concentrations who were receiving a multiple insulin injection regimen. One patient withdrew immediately after recruitment.


METHODS
After an overnight fast patients received 96 nmol (16 IU insulin) of either 125I-NovoSol Basal or 125I-Ultratard HM injected subcutaneously into the thigh. To ensure that the insulin entered the subcutaneous fat at the same depth, ultrasonography was performed on each patient before the first injection. A different injection site on the thigh was used each day for four days in order to facilitate monitoring of the disappearance of four different depots in each patient.


METHODS
Residual activity at the injection site was measured roughly every two hours throughout the day. No radioactivity measurements were performed overnight (10 pm till 8 am). The residual radioactivity after the injection on the first day (upper right thigh) was recorded for five days, that after the injection on the second day (upper left thigh) for four days, after the injection on the third day (lower right thigh) for three days, and after the last injection (lower left thigh) for two days.


RESULTS
NovoSol Basal was absorbed according to first order kinetics with a mean t50% of 35.3 (SEM 1.4) hours; Ultratard HM was absorbed after a lag phase and the corresponding t50% was 25.5 (2.5) hours. The intraindividual variations in t50% were significantly smaller with NovoSol Basal than with Ultratard HM (18.4% v 44.5%; p less than 0.001). Interindividual variations, however, were not significantly different (25.2% v 36.9%; p = 0.38). The total variation in t50% was substantially smaller with NovoSol Basal than with Ultratard HM (20.3% v 42.8%).


CONCLUSIONS
NovoSol Basal seems to be an appreciable advance over Ultratard HM as a soluble insulin preparation for obtaining reproducible 24 hour insulin concentrations in the blood
Jørgensen
S
S
Novo Research Institute, Copenhagen, Denmark.
Vaag
A
A
Langkjaer
L
L
Hougaard
P
P
Markussen
J
J
D000042:Absorption; D003692:Delayed-Action Preparations; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004341:Drug Evaluation; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D049528:Insulin, Long-Acting; D011897:Random Allocation; D011994:Recombinant Proteins
D003692:Delayed-Action Preparations; D007328:Insulin; D049528:Insulin, Long-Acting; C023501:Insulin, Ultratard; D011994:Recombinant Proteins; C061395:NovoSol Basal insulin