A Comparison of the Steady-State Pharmacokinetic and Pharmacodynamic Profiles of 100 and 200 U/mL Formulations of Ultra-Long-Acting Insulin Degludec

作者：Korsatko Stefan; Deller Sigrid; Koehler Gerd; Mader Julia K; Neubauer Katharina; Adrian Charlotte L; Thomsen Henrik; Haahr Hanne; Pieber Thomas R^*

来源：Clinical Drug Investigation, 2013, 33(7): 515-521.

DOI：10.1007/s40261-013-0096-7

Insulin degludec (IDeg) is a new-generation basal insulin that forms soluble multi-hexamers upon subcutaneous injection, resulting in a depot from which IDeg monomers are slowly and continuously absorbed to provide an ultra-long action profile. This double-blind, crossover, randomized study compared the pharmacokinetic and pharmacodynamic properties between IDeg 100 U/mL (U100) and IDeg 200 U/mL (U200) under steady-state (SS) conditions in subjects with type 1 diabetes mellitus. %26lt;br%26gt;Participants (n = 33 adults) underwent 8-day treatment periods with 0.4 U/kg IDeg U100 and IDeg U200 given once daily with insulin aspart at mealtimes. On day 8, a 26-h euglycaemic glucose clamp (5.5 mmol/L) was performed. %26lt;br%26gt;The concentration-time profiles of IDeg U100 and IDeg U200 were similar, and a post-hoc analysis showed bioequivalence between these formulations, as the 90 % confidence intervals (CIs) of the U200/U100 ratios for area under the steady-state serum IDeg concentration-time curve during a dosing interval (tau; 0-24 h) (AUC(tau,SS,IDeg)) (0.99 [0.91-1.07]) and maximum steady-state IDeg concentration during a dosing interval (tau) (C (max,SS,IDeg)) (0.93 [0.84-1.02]) were within the interval 0.80-1.25. Comparable glucose infusion rates (GIR) were observed for IDeg U100 and IDeg U200 (AUC(tau,SS,GIR) [mg/kg]: 2,255 vs. 2,123) and the mean ratio (95 % CI) of IDeg U200/U100 for the primary endpoint (AUC(tau,SS,GIR)) was 0.94 [0.86-1.03]. For both formulations, the glucose-lowering effect of IDeg was evenly distributed between the first and second 12 h post-dosing (U100: AUC(12,SS,GIR)/AUC(24,SS,GIR) = 48 %; U200: AUC(12,SS,GIR)/AUC(24,SS,GIR) = 46 %). Both formulations were well tolerated, and no safety events of significance were identified. %26lt;br%26gt;IDeg U100 and U200 formulations are bioequivalent and have similar pharmacodynamic profiles at SS, implying that they can be used interchangeably in clinical practice.

• 出版日期2013