A time-dependent volume of distribution term used to describe linear concentration-time profiles

The present study was conducted to develop, test, and apply a single exponential time-dependent volume of distribution function to describe the pharmacokinetics of compounds following instantaneous, zero-order and first order input. Simulations were used to show the applicability and flexibility of the equations. Experimental data from the literature were fitted using the equations developed in the present study. In addition, the results of these fitted curves were compared to the results of the original fitting procedures to compare and contrast the methods. In the present analysis, the change from an initial volume (V1) to the total volume (V T) is perceived as a simple exponential function. Therefore, a single exponential term to describe elimination and a single exponential term to describe the change from V1 to V T were used to describe the entire blood concentration profile. The results from present simulations and fitted data indicate that the transition from V1 to V T is a more continuous process than observed with classical methods and is consistent with results obtained from physiologic flow-limited models. This observation suggests that the present curve-fitting technique may be more akin to physiologic reality, in that it depicts the change from the initial volume of distribution to the total volume of distribution as a continuous exponential function which reflects the establishment of an equilibrium.