Pharmacokinetic models of the metabolism of foreign compounds may be used to identify relevant parameters that govern the time course of chemically reactive metabolites at putative action sites and to aid in the development of experiments by which these parameters may be estimated. During the past year pharmacolinetic equations have been derived to describe the formation and elimination of the chemically reactive metabolite of acetaminophen in liver. The equations include not only the elimination of acetaminophen by various pathways, but also the effect of the reactive metabolite on the concentration of glutathione in liver. These equations revealed ways of estimating the hepatic clearance for the formation of the reactive metabolite in living animals. They thus illustrate a way of comparing the in vitro and in vivo activities of the enzymes that catalyze the formation of certain kinds of chemically reactive metabolites, which would be difficult, if not impossible, to obtain by direct experimentation.
