title: Pharmacokinetics and pharmacodynamics of different modes of insulin pump delivery. A randomized, controlled study comparing subcutaneous and intravenous administration of insulin aspart.
abstract: OBJECTIVE
  To study the pharmacokinetics and pharmacodynamics of three different modes of insulin infusion delivered by means of an insulin pump: subcutaneous bolus insulin injection once an hour, continuous subcutaneous insulin infusion and continuous intravenous insulin infusion.
  
  
  METHODS
  In random order, ten patients with Type 1 diabetes mellitus received insulin aspart with subcutaneous bolus insulin injection, continuous subcutaneous insulin infusion and continuous intravenous insulin infusion. The insulin aspart doses were individualized.
  
  
  RESULTS
  A non-random, sinus-like variation of serum insulin aspart over time was found with subcutaneous bolus insulin injection compared with continuous subcutaneous insulin infusion and continuous intravenous insulin infusion (P<0.0001). Random variation of serum insulin aspart over time was significantly higher with continuous intravenous insulin infusion compared with subcutaneous bolus insulin injection (P=0.023) and continuous subcutaneous insulin infusion (P=0.013). Mean serum insulin aspart did not differ significantly between subcutaneous bolus insulin injection, continuous subcutaneous insulin infusion and continuous intravenous insulin infusion (P=0.17). Thus, absolute bioavailability was near 100% for both subcutaneous bolus insulin injection and continuous subcutaneous insulin infusion. Statistically significant differences were seen in mean plasma glucose and mean glucose infusion rate, with the highest mean plasma glucose and the lowest mean glucose infusion rate with continuous intravenous insulin infusion, suggesting a slightly lower bioefficacy of continuous intravenous insulin infusion compared with subcutaneous bolus insulin injection and continuous subcutaneous insulin infusion.
  
  
  CONCLUSIONS
  Small but statistically significant differences in pharmacokinetics and pharmacodynamics between subcutaneous bolus insulin injection, continuous subcutaneous insulin infusion and continuous intravenous insulin infusion were observed. However, no major clinically relevant differences were found, suggesting that, for a basal subcutaneous insulin aspart pump therapy, relatively infrequent pump stroke frequency may suffice.
authors.affiliation: Department of Endocrinology M, Aarhus Sygehus NBG, Aarhus University Hospital, Noerrebrogade 44, Aarhus, Denmark. charlotte.ihlo@dadlnet.dk
authors.forename: C A
authors.initials: CA
authors.lastname: Ihlo
authors.forename: T
authors.initials: T
authors.lastname: Lauritzen
authors.forename: J
authors.initials: J
authors.lastname: Sturis
authors.forename: O
authors.initials: O
authors.lastname: Skyggebjerg
authors.forename: J S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: T
authors.initials: T
authors.lastname: Laursen
mesh_terms: D000328:Adult; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D055104:Infusions, Subcutaneous; D007328:Insulin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D061267:Insulin Aspart; D007332:Insulin Infusion Systems; D008297:Male
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart