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Time‐action profile of the soluble, fatty acid acylated, long‐acting insulin analogue NN304
Author(s) -
Heinemann L.,
Sinha K.,
Weyer C.,
Loftager M.,
Hirschberger S.,
Heise T.
Publication year - 1999
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1046/j.1464-5491.1999.00081.x
Subject(s) - medicine , insulin , pharmacodynamics , endocrinology , nph insulin , pharmacokinetics , diabetes mellitus , hypoglycemia , insulin glargine
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 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 (AUC 0–1440 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: GIR max 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 t max (446 ± 162 vs. 359 ± 175 min) and lower AUC 0–240 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 (AUC 0–720 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 (AUC 0–1440 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 in its metabolic effect. Diabet. Med. 16, 332–338 (1999)