A decision tree approach for the application of drug metabolism and kinetic studies to in vivo and in vitro toxicological and pharmacological testing.
The integration of toxicological and other biological findings with information on drug metabolism and pharmacokinetics is often very important for rational decision making in safety evaluation programmes. This goal is unlikely to be achieved by conducting a routine package of inflexibly defined drug metabolism and pharmacokinetic test protocols for each new chemical. Rather, an intelligent selection of experiments based on the known properties of a chemical is required. A series of decision trees are proposed which serve as an aide memoire in the choice of appropriate drug metabolism and pharmacokinetic experiments. These decision trees cover the physicochemical properties of a chemical, data on animal and human pharmacology and toxicology, and environmental information relevant to possible contamination. In many cases, drug metabolism and pharmacokinetic factors are an important prerequisite to the design of in vitro tests that are relevant to the in vivo situation. A scheme is provided to assist the identification of appropriate conditions for the in vitro testing of individual chemicals.
D000818:Animals; D003201:Computers; D046508:Culture Techniques; D003657:Decision Making; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004785:Environmental Pollutants / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008954:Models, Biological; D008970:Molecular Weight; D009924:Organ Culture Techniques; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D011955:Receptors, Drug / Q000378:metabolism; D012377:Rodentia
D004785:Environmental Pollutants; D004364:Pharmaceutical Preparations; D011955:Receptors, Drug