General method for evaluating the fraction of the irreversible organ clearance due to conversion of drug to a primary metabolite.

An expression for the fractional metabolic clearance of a drug across an organ has been developed. The expression is a function of areas under the temporal profiles of the drug and metabolite concentrations in the sampling compartment. Formation of the metabolite of interest is permitted throughout the linear systems analyzed. The expression is shown to be applicable to any linear system provided there is only a single direct feed from the organ of interest (compartment where formation of the particular metabolite is being investigated) to the drug-sampling compartment.