System-based Approach to Prediction of Surfactants’ Influences on Pharmaco-kinetics and Pharmacodynamics

Abstract

Abstract The paper presents a system-based approach for predicting the changes of the plasma concentration and the therapeutic effect of sodium p-aminosalicylate caused by addition of surfactant Tween 80 to a liquid dosage form. A predictive pharmacokinetic model of the oral administration is synthetized together with the corresponding model of its parametric sensitivity. The sensitivities predicted by the model are then compared to those obtained from the in-vi vo experiment. The close correspondence between them is used to prove the model correctness. Similarly the Emax model of the therapeutic effect predicts influences of the added surfactants on the therapeutic effect. In this context, the problem of determining an optimal absorption rate for the desired time course of the therapeutic effect is solved. As a by-product this study, it is shown that the (in-silico generated) sensitivity of plasma concentration to the drug absorption rate may provide information on how far the in-silico experiment can serve as a substitute for in-vivo bioavailability and bioequivalence studies