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


CONCLUSIONS
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.
Petersen
S B
SB
Novo Nordisk A/S, Diabetes Research Unit, 2760 Maaloev, Denmark.
Kildegaard
J
J
Nielsen
F S
FS
Søndergaard
E
E
Parkner
T
T
Laursen
T
T
Lauritzen
T
T
Skyggebjerg
O
O
Christiansen
J S
JS
D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D018592:Cross-Over Studies; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood*; D061267:Insulin Aspart; D007332:Insulin Infusion Systems; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart