Time-action profile of the soluble, fatty acid acylated, long-acting insulin analogue NN304.

摘要: Summary Aims To compare the pharmacokinetic and pharmacodynamic properties of subcutaneously injected NN304, a novel long-acting insulin analogue, to NPH-insulin during euglycaemic glucose clamps in 11 healthy volunteers. Methods On three study days NN304 was different doses (0.15, 0.3, 0.6 U/kg body weight), while (0.3 U/kg) identical dose on two other days. Results Injection resulted linear proportional increase total concentrations (AUC0–1440 min: 0.15 U/kg: 344 ± 43, 0.3 U/kg: 666 ± 82, 0.6 U/kg: 1295 ± 210 nmol/l; P < 0.001). Maximal (609 ± 140, 1046 ± 283, 2033 ± 460 pmol/l; P < 0.001) were reached after 4–6 h. The metabolic response (expressed as maximal infusion rates (GIR)) induced by subcutaneous injection did not show pronounced peak seen with an dose: GIRmax 3.2 ± 1.1 vs. 4.4 ± 1.8 mg/kg/min (P < 0.05 for 0.3 U/kg NPH-insulin; mean both NPH-insulin, all others significant). also showed slower onset action, indicated significantly higher tmax (446 ± 162 359 ± 175 min) lower AUC0–240 min (0.5 ± 0.3 0.8 ± 0.4 g/kg/240 min; P < 0.05, respectively). consumption first 720 min (AUC0–720 min 1.1 ± 0.6, 1.9 ± 0.8, 1.7 ± 0.8 g/kg; P < 0.05 0.15 U/kg), but over whole period (AUC0–1440 min 1.8 ± 1.1, 3.1 ± 1.3, 2.8 ± 1.4 g/kg). Conclusions at concentration dose–response effect more even than NPH-insulin. However, we found no clear its effect. Diabet. Med. 16, 332–338 (1999)