Using Gaussian-like input rate function in the two-compartment model. Formulation and application to analysis of didanosine plasma concentration in two Japanese hemophiliacs.

Abstract

We used a time-dependent input rate function in the two-compartment model to simulate drug plasma concentrations after an oral administration. The input rate term has a Gaussian-like structure with two parameters, time to maximum absorption rate (tm) and measure of the duration of the absorption process (s). This structure corresponds to the scenario in which the absorption rate of the drug into the central compartment changes unimodally with respect to time after administration with a single peak at time tm. We demonstrate the applicability of this formulation in the simulation of plasma concentration of didanosine after oral administration in two Japanese hemophiliacs. We found that we were able to simulate the time courses of the didanosine plasma concentrations in both patients using the theoretical equation with the input term included, and that we were able to determine the six parameters in the equation by the least squares estimation. Pharmacokinetic values derived from the best-fit curve were almost comparable to those reported in other literature except that the Cmax and AUC0-infinity seemed to be slightly higher than those reported elsewhere. Although we are unable to verify the accuracy of this formulation because of the lack of sufficient Japanese data, we are able to demonstrate its efficacy and convenience in the application presented here.