Comprehensive pharmacokinetic model of insulin Glargine and other insulin formulations.

In this paper, a comprehensive pharmacokinetic model for different insulin formulations including insulin Glargine is developed based on the model proposed by Trajanoski et al. (1993). Current models show limitations for insulin Glargine due to the appearance of an uncharacteristic peak in the concentration-time evolution of plasma insulin that does not coincide with real experimental data. This important limitation has been solved in this paper by introducing a new virtual insulin state called the bound state, in addition to the dimeric and hexameric ones. Trying to describe the retarded action of insulin Glargine, the modeling idea behind this approach is that immediately after the subcutaneous injection all the insulin resides in the bound state, and only then small amounts of insulin in the hexameric form disengage from the bound state. For the model evaluation different simulation results are compared. Using experimental data published by Lepore et al. (2000), the developed model turned out to be capable of at least qualitatively predicting the concentration-time profile of plasma insulin. Both exogenous insulin flow simulations and spatial diffusion simulations show the plausibility and correct implementation of the derived model. Considering all these simulation results, the here presented new pharmacokinetic model demonstrates to be able to reproduce real patient behavior simulating even complete insulin regimes including long-acting, intermediate and short-acting insulin formulations.

A novel method for continuous online glucose monitoring in humans: the comparative microdialysis technique.

The aim of this study was to prove the feasibility of continuous subcutaneous glucose monitoring in humans using the comparative microdialysis technique (CMT). The performance of the CMT was determined by comparing tissue glucose values with venous or capillary blood glucose values in healthy volunteers and type 1 diabetic subjects. The CMT is a microdialysis-based system for continuous online glucose monitoring in humans. This technique does not require calibration by the patient. Physiological saline with glucose (5.5 mM) is pumped in a stop-flow mode through a microdialysis probe inserted into the abdominal s.c. tissue. Tissue glucose concentration is calculated by comparing the dialysate and perfusate glucose concentrations. The time delay due to the measurement process is 9 min. We tested the CMT on six healthy volunteers and six type 1 diabetic patients for 24 h in our clinical setting. Comparisons were made to HemoCue analyzer (Angelholm, Sweden) capillary blood glucose measurements (healthy volunteers) and to venous blood glucose concentration determined with a Hitachi analyzer (diabetic patients). The mean absolute relative error of the CMT glucose values from the blood glucose values was 17.8+/-15.5% (n = 167) for the healthy volunteers and 11.0+/-10.8% (n = 425) for the diabetic patients. The mean difference was 0.42+/-1.06 mM (healthy volunteers) and -0.17+/-1.22 mM (diabetic patients). Error grid analysis for the values obtained in diabetic patients demonstrated that 99% of CMT glucose values were within clinically acceptable regions (regions A and B of the Clarke Error Grid). The study results show that the CMT is an accurate technique for continuous online glucose monitoring.