Essay --

Pharmacokinetic (PK) modelling plays a critical role in drug discovery and clinical pharmacotherapy of several types of drugs. PK modelling and simulation approach have been widely use to explain and predict PK profile of a drug. Several PK simulations are employed to measure estimated therapeutic window, dose selection, and to identify mechanism of action of chemicals and their metabolites in various tissues throughout the body. This integral component of drugs development process can be employed to investigate hepatic deposition of substrates. The data generated from such trial may be used to predict substrate deposition in vivo or to extrapolate deposition from animal to humans. For instance, measurement of transhepatic extraction in the isolated perfused rat liver permits assessment of hepatic clearance in vivo as the product of extraction and hepatic blood flow, assuming the flow is known. Hepatic clearance can them be predicted across mammalian species through incorporation of extraction into physiologically based PK models (Dedrick, 1974). There are different approaches to ph...