Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes.
OBJECTIVE
This trial aimed to characterize for the first time the pharmacokinetic profile of insulin detemir, the novel soluble basal insulin analog, in children and adolescents compared with adults. Comparisons were also made with NPH insulin to determine any between-treatment difference in the effect of age on pharmacokinetic profile.


METHODS
This single-center, open-label, randomized, crossover trial included children (aged 6-12 years, n = 13), adolescents (aged 13-17 years, n = 10), and adults (aged 18-65 years, n = 11) of both sexes. Subjects were given single doses of 0.5 units/kg s.c. insulin detemir or 0.5 IU/kg NPH insulin on 2 separate days. Serial blood sampling was performed for 24 h for analysis of serum insulin detemir, human insulin, and glucose concentrations.


RESULTS
The mean pharmacokinetic profile of insulin detemir was similar across all three age-groups. This was determined by statistical analyses of the data, which showed no overall age effect or between-group differences when pairwise comparisons were made between children (or adolescents) and adults on the parameters of the area under the curve (AUC), AUC from zero to infinity, AUC from 0 to 24 h [AUC((0-24 h))], and the maximum concentration measured during the 24 h after closing. No overall age effect for AUC((0-24 h)) and C(max) was detected for NPH insulin, but data were only analyzable from seven adults and pairwise comparisons did indicate that children and adults had different pharmacokinetic profiles. Less total variability in the pharmacokinetics of insulin detemir than NPH insulin was indicated by lower coefficients of variation in AUC, C(max), and time to maximum concentration in all three age-groups.


CONCLUSIONS
The data suggest that insulin detemir can be used in children and adolescents with type 1 diabetes using titration guidelines similar to those used in adults. Moreover, insulin detemir may offer the advantage of greater predictability of response in comparison to NPH insulin due to lower total variability and a lesser degree of kinetic disparity across age-groups.
Kinderkrankenhaus auf der Bult, Hannover, Germany. danne@hka.de
Thomas
T
Danne
Kerstin
K
Lüpke
Kerstin
K
Walte
Wolfgang
W
Von Schuetz
Mari-Anne
MA
Gall
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002352:Carrier Proteins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D000069057:Insulin Detemir; D007336:Insulin, Isophane / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged
D002352:Carrier Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir; D007336:Insulin, Isophane