Multifactorial modeling, drug interactions, liver damage and aging.

Abstract

A well designed physiological flow model can be used not only to describe and analyze the basic elimination of a drug but also it can form the basis for multifactorial analysis in situations of multiple organ dysfunction and drug therapy. Physiological flow models use existent knowledge of anatomical structure and physiological processes along with the biochemical basis of drug elimination to calculate concentration-vs-time profiles of drugs in various organs and tissue regions. A tissue region or organ must be included in the model if it is an important site of storage, toxicity, elimination, or other significant pharmacological action. Such models can be a powerful tool in medicine providing a rational basis for multiple drug therapy in high risk patients with altered organ function--especially for drugs with a narrow margin of safety. For some specific types of drug systems, physiological flow model models exist which can accurately describe drug concentration profiles in tissues for a variety of situations. A definitive general model is theoretically possible; but, in practice, has not yet been developed. Future research could provide the necessary information to make multifactorial analysis a clinically useful tool in rational drug therapy.