The Pharmacokinetics of Insulin After Continuous Subcutaneous Infusion or Bolus Subcutaneous Injection in Diabetic Patients

Abstract

Pharmacokinetic models of insulin were examined in order to describe a plasma concentration-time profile after subcutaneous (s.c.) administration of insulin to the patients with insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM). Diabetic subjects were restricted to those with fasting plasma insulin levels around the lowest limit for insulin assay (5 microU/ml). A one-compartment open model with first-order absorption and elimination was appropriate for estimating the plasma concentration-time profile of insulin injected or infused subcutaneously. In the case of continuous s.c. insulin infusion (CSII) for 1 h at the rate of 3 ml/h (2--3 U/ml), the absorption rate constant (Ka), elimination rate constant (Ke), and distribution volume (Vd) were 0.026 +/- 0.001 min-1 (mean +/- SEM; absorption half-life: 27 min), 0.013 +/- 0.005 min-1 (elimination half-life: 53 min), and 1.99 +/- 0.49 L/kg body wt, respectively. These values did not differ significantly from those generated by single bolus s.c. injection of undiluted insulin (40 U/ml). The calculated areas under the plasma insulin concentration-time curves from time zero to infinity ([AUC] 0 infinity) did not differ after each mode of administration, while the [AUC] 0 infinity after CSII was about 32% of that following intravenous bolus injection (P less than 0.01). The following conclusions can be drawn from these results: (1) the plasma concentration-time profile of insulin after CSII…