Pharmacokinetic factors governing the steady-state concentrations of foreign chemicals and their metabolites.
It is well known that various environmental chemicals can either increase or decrease the activities of enzymes that metabolize foreign compounds and their metabolites. In addition, changes in the activities of these enzymes can alter the concentration of the foreign compounds and metabolites in tissues. However, the theoretical basis by which we can quantitatively relate a change in the activity of a given enzyme to a change in the concentrations of these compounds remains in its infancy. In some instances, the change in concentration of a foreign compound or metabolite will be inversely proportional to the change in the enzyme activity. But in other instances, marked changes in enzyme activity may result in only trivial changes in the concentration of the compounds and their metabolites at sites of action. Pharmacokinetics provide a means for testing the validity of our concepts of how the concentrations of foreign compounds and their metabolites depend on enzyme activities, rates of excretion by the kidneys and lung, reversible binding to tissue components, rates of diffusion across cellular membranes, blood flow rates and the sites of administration. The present paper presents mathematical equations that show the effects of the route of administration on the steady-state concentrations of foreign compounds and their metabolites in tissues when the substances are metabolized by the liver and excreted by the kidney. These equations are especially relevant to studies of chemically reactive metabolites.
D000818:Animals; D001711:Biotransformation; D004247:DNA / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008433:Mathematics; D008954:Models, Biological; D010477:Perfusion; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012313:RNA / Q000378:metabolism
D004364:Pharmaceutical Preparations; D012313:RNA; D004247:DNA