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 μU/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) did not differ after each mode of administration, while the [AUC] ∞0 after CSII was about 32% of that following intravenous bolus injection (P < 0.01). The following conclusions can be drawn from these results: (1) the plasma concentration-time profile of insulin after CSII or bolus s.c. injection can be analyzed by pharmacokinetic modeling, (2) the absorption kinetics of insulin did ot differ significantly between two modes of s.c. insulin administration in the patients with IDDM or NIDDM, and (3) the insulin after CSII or single bolus s.c. injection seems to be degraded at the s.c. site to the same extent.