Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue NN304 in comparison to NPH insulin in humans.

摘要: Abstract NN304 is a long-acting insulin analogue that acylated with 14-C-fatty acid chain. Protraction of action this novel due not to slow absorption after subcutaneous administration but reversible binding albumin. We investigated the pharmacokinetic and pharmacodynamic properties (0.3 0.6 U/kg) in comparison NPH IU/kg) 10 healthy volunteers performing randomised, double-blind, cross-over, placebo-controlled glucose clamp study. During observation period 24 hours areas under curve for NPH[0.3 IU/kg] vs. NPH[0.6 were 60 102 nmol min l(-1) (p<0.01) NN304[0.3 U/kg] NN304[0.6 490 932 (p <0.001), suggesting clear dose-response relationship both NN304. The amount disposed (area infusion) differed statistical significance between five treatments was highest (2671 mg/kg) lowest placebo (265 mg/kg). However, area infusion treatment only 36% (dose 0.3 24% observed corresponding doses insulin. Moreover, increasing dosages failed demonstrate significant regard infusion. This study demonstrates principle protracted by albumin effective humans albeit at much lower rate utilisation when compared Thus, contrast animal studies can be considered equipotent humans.