Pharmacokinetics following continuous subcutaneous insulin infusion of insulin aspart with or without initial subcutaneous bolus

Aim: To evaluate time to steady state insulin concentration (C SS ) following continuous subcutaneous insulin infusion (CSII) of insulin aspart (IAsp) with or without an initial s.c. bolus. Methods: in random order 10 healthy volunteers were given a basal insulin infusion rate (0.5 U/h) for 8 h with or without an initial s.c. bolus (1.4 U). Serum IAsp was measured until 3 h after infusion was stopped. Results: An overshoot of IAsp was seen before C SS was achieved following an initial bolus of insulin as compared to no bolus. The apparent half-life (t ½ ) with or without bolus did not differ (p = 0.15). Time to steady state (T SS ) was evaluated in two ways: (1) T SS defined as the first point within an interval of C SS ± 2 x CV was 233 vs. 166 min with and without a bolus respectively (p = 0.068). (2) A t-test was performed for each concentration-time point vs. mean C SS , and the first point with no significance was defined, T SS . This gave 208 (p = 0.09) and 178 min (p = 0.24) with and without bolus respectively. Mathematical modelling suggests that an ideal mean bolus should be 0.89 U, and that this bolus dose may result in a shorter T SS . Conclusion: A bolus of 1.4 U resulted in an overshoot of serum IAsp before C SS and a longer period before C SS is achieved. Mathematical modelling suggests that a mean bolus of 0.89 U would result in a faster achievement of C SS compared to no bolus.