Poster Presenter

In Silico Analysis of Human Pharmacokinetics Using a Threecompartment Model
Mukesh Doble and C. Naveen
India

Bioavailability is a vital factor determining thes efficacy of the drugs and their cost. Substantial number of potential lead molecules is eliminated because of poor bioavailability. The In vivo methods for the prediction of bioavailability are tedious, time consuming and expensive. In this paper, an in silico pharmacokinetic approach for predicting Oral Bioavailability using a three-compartment model is reported. The central compartment represents the blood and the concentration in this compartment gives the bioavailability at a given time point. The drug is first absorbed into this compartment which is controlled by the absorption constant, and subsequently is distributed into two peripheral compartments, representing highly perfused tissues, where drug distribution is fast, and muscles and adipose tissues, where distribution is slow. The reversible distribution between the central and each of the peripheral compartments is governed by the inter compartmental constants. The elimination, finally, takes place from the central compartment controlled by the elimination constant. The constant values for absorption, elimination and transfer in and out of compartment where distribution is fast are obtained by developing structure property relationships of the data reported in the literature. The values for the constants representing movement in and out of the slow compartment are tuned to predict concentration-time profiles of the drugs reported in literature and compared with the experimental data.