NovoSol Basal: Pharmacokinetics of a novel soluble long acting insulin analogue

Abstract

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. Design - 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. Setting - Referrals to the diabetes research centre in Hvidore, Copenhagen. Patients - Eight insulin dependent (type I) diabetics with low or detectable C peptide concentrations who were receiving a multiple insulin injection regimen. One patient withdrew immediately after recruitment. Interventions - 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. Main outcome measure - 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 t(50%) of 35.3 (SEM 1.4) hours; Ultratard HM was absorbed after a lag phase and the corresponding t(50%) was 25.5 (2.5) hours. The intraindividual variations in t(50%) were significantly smaller with NovoSol Basal than with Ultratard HM (18.4% v 44.5%; p < 0.001). Interindividual variations, however, were not significantly different (25.2% v 36.9%; p = 0.38). The total variation in t(50%) 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 after once daily injection.