Fluctuation and reproducibility of exposure and effect of insulin glargine in healthy subjects.
OBJECTIVE
Low diurnal fluctuation and high day-to-day reproducibility in exposure and effect characterize beneficial basal insulin products. Two insulin glargine (LANTUS) formulations [without (R) or with polysorbate-20 (T)], added to minimize unfolding of proteins and subsequent formation of fibril structures, were assessed for equivalence in exposure and effect, and aspects of fluctuation and reproducibility in time-concentration and time-action profiles.


METHODS
A dose of 0.4 U/kg was subcutaneously administered to 24 healthy subjects in a two-sequence (R-T-R-T or T-R-T-R), randomized, four-way crossover trial utilizing 30-h Biostator-based euglycaemic glucose clamps.


RESULTS
Identical serum insulin glargine concentration and time-action profiles established average, individual and population equivalence in insulin exposure and effect. Point estimates for 24-h area under the curve for insulin (INS-AUC(0-24) (h)) and glucose infusion rates (GIR-AUC(0-24) (h)) were 97% [90% confidence interval (CI): 91-103%] and 100% (88-114%), respectively. Within-subject variability (coefficient of variation) for INS-AUC(0-24) (h) and GIR-AUC(0-24) (h) were 19% (95% CI: 14-25%) and 34% (24-43%), respectively. The diurnal relative fluctuation of the serum insulin glargine concentration was 20% (95% CI: 19-21%).


CONCLUSIONS
Insulin glargine in either formulation presents with a high day-to-day reproducibility of a uniform release after injection enabling an effective basal insulin supplementation.
Becker
R H A
RH
Sanofi-Aventis Pharma Deutschland GmbH, Frankfurt, Germany.
Frick
A D
AD
Teichert
L
L
Nosek
L
L
Heinemann
L
L
Heise
T
T
Rave
K
K
D000328:Adult; D000367:Age Factors; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis*; D015992:Body Mass Index; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005079:Excipients; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged; D011136:Polysorbates; D013997:Time Factors; D055815:Young Adult
D001786:Blood Glucose; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D011136:Polysorbates; D000069036:Insulin Glargine