Effect of physicochemical variables of regular insulin formulations on their absorption from the subcutaneous tissue.
BACKGROUND
Physicochemical properties of regular insulin formulations influence the subcutaneous absorption kinetics.


OBJECTIVE
To compare the subcutaneous absorption of regular insulin formulations with different concentration, temperature and hexamer-aggregation.


METHODS
In random order, 24 fasting healthy men were injected with identical doses of regular human insulin in concentrations of 40 units/ml (U40), 100 units/ml (U100), and the insulin analogue Lispro; regular human insulin U100 was applied at either 8, or 37 degrees C. Insulinaemia, C-peptide and plasma glucose levels were monitored for every 15 min up to 45 min after the injection.


RESULTS
In comparison to U100 human regular insulin, Lispro induced significantly higher insulinaemia 15-45 min after injection. In comparison to U40 insulin, however, insulinaemia was higher only at 15 and 30 min after injection, and was comparable at 45 min (210 +/- 11 pmol/l after Lispro versus 191 +/- 15 pmol/l after U40 regular insulin; P > 0.06). There was no difference in insulinaemia between U100 regular insulin of 8 or 37 degrees C. C-peptide and plasma glucose levels were altered accordingly.


CONCLUSIONS
Assuming identical clearance rates of human insulin and Lispro, our data show that insulin absorption is substantially increased by reduced hexamer-aggregation (e.g. with insulin analogue Lispro), when compared to U100 regular human insulin. It is only marginally better, when compared to U40 regular human insulin. The increase in insulin temperature from 8 to 37 degrees C had no effect on the respective absorption kinetics.
Medical Department of Metabolic Diseases and Nutrition, Heinrich-Heine-University of Düsseldorf, Germany.
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Polaschegg
D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D007328:Insulin / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics*; D061268:Insulin Lispro; D008297:Male; D012016:Reference Values; D012869:Skin Absorption
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro