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. Aim of study: To comp are the subcutaneous absorption of regular insulin formulations with d ifferent concentration, temperature and hexamer-aggregation. Study des ign: In random order, 24 fasting healthy men were injected with identi cal doses of regular human insulin in concentrations of 40 units/ml (U 40), 100 units/ml (U100), and the insulin analogue Lispro; regular hum an 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, insulin aemia was higher only at 15 and 30 min after injection, and was compar able 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 ins ulinaemia between U100 regular insulin of 8 or 37 degrees C. C-peptide and plasma glucose levels were altered accordingly. Conclusion: Assum ing identical clearance rates of human insulin and Lispro, our data sh ow that insulin absorption is substantially increased by reduced hexam er-aggregation (e.g. with insulin analogue Lispro), when compared to U 100 regular human insulin. It is only marginally better, when compared to U40 regular human insulin. The increase in insulin temperature fro m 8 to 37 degrees C had no effect on the respective absorption kinetic s. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.