INFLUENCE OF ADMINISTRATION ROUTE AND BLOOD-SAMPLING SITE ON THE AREA UNDER THE CURVE - ASSESSMENT OF GUT WALL, LIVER, AND LUNG METABOLISM FROM A PHYSIOLOGICAL MODEL

Abstract

A pharmacokinetic perfusion-limited model was developed to describe the change of drug concentrations across several eliminating compartments such as lung, liver and gut wall and a noneliminating central (or blood) compartment. The model holds only for linear kinetics. Using this model, it is possible to assess liver, lung and gut wall metabolism by comparing areas under the blood concentration vs. time curves aftr administration of the drug either intra-arterially, i.v., via the portal vein or orally (duodenal administration). These comparisons provide a basis to decide whether drug metabolism occurs in the liver and/or extrahepatic tissues and illustrate the effects of different administration routes on these areas. The areas under the blood concentration-time curves are dependent on the blood-sampling site. The model can be helpful, to a limited extent, in relating in vivo determined intrinsic clearances to in vitro obtained enzymatic parameters.