Pharmacokinetics following continuous subcutaneous insulin infusion of insulin aspart with or without initial subcutaneous bolus.
Author(s): Petersen SB, Kildegaard J, Nielsen FS, Sondergaard E, Parkner T, Laursen T, Lauritzen T, Skyggebjerg O, Christiansen JS
Affiliation(s): Novo Nordisk A/S, Diabetes Research Unit, 2760 Maaloev, Denmark.
Publication date & source: 2010-04, Diabetes Obes Metab., 12(4):334-40.
Publication type: Randomized Controlled Trial
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((1/2))) 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.