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.