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- Title
Time-action profile of the soluble, fatty acid acylated, long-acting insulin analogue NN304.
- Authors
Heinemann, L.; Sinha, K.; Weyer, C.; Loftager, M.; Hirschberger, S.; Heise, T.
- Abstract
SummaryAims 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 injected in three different doses (0.15, 0.3, 0.6 U/kg body weight), while NPH-insulin (0.3 U/kg) was injected in identical dose on two other days. Results Injection of NN304 resulted in a linear and proportional increase in total NN304 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 concentrations (609 ± 140, 1046 ± 283, 2033 ± 460 pmol/l; P < 0.001) were reached after 4–6 h. The metabolic response (expressed as maximal glucose infusion rates (GIR)) induced by subcutaneous injection of NN304 did not show the pronounced peak seen with NPH-insulin in an identical dose: GIRmax 3.2 ± 1.1 vs. 4.4 ± 1.8 mg/kg/min (P < 0.05 for 0.3 U/kg NN304 vs. NPH-insulin; mean of both study days with NPH-insulin, all others not significant). NN304 also showed a slower onset of action, as indicated by a significantly higher tmax (446 ± 162 vs. 359 ± 175 min) and lower AUC0–240 min (0.5 ± 0.3 vs. 0.8 ± 0.4 g/kg/240 min; P < 0.05, respectively). The three different doses of NN304 induced a significantly different glucose consumption in the first 720 min after injection (AUC0–720 min 1.1 ± 0.6, 1.9 ± 0.8, 1.7 ± 0.8 g/kg; P < 0.05 for 0.15 U/kg), but not over the whole study period (AUC0–1440 min 1.8 ± 1.1, 3.1 ± 1.3, 2.8 ± 1.4 g/kg). Conclusions Injection of NN304 at different doses resulted in an increase in total NN304 concentration in a linear dose–response effect and a more even metabolic effect than NPH-insulin. However, we found no clear dose–response...
- Subjects
INSULIN derivatives; HYPOGLYCEMIC agents; TREATMENT of diabetes; PHARMACOKINETICS; BIOCHEMICAL mechanism of action
- Publication
Diabetic Medicine, 1999, Vol 16, Issue 4, p332
- ISSN
0742-3071
- Publication type
Article
- DOI
10.1046/j.1464-5491.1999.00081.x