Metabolite pharmacokinetics: the area under the curve of metabolite and the fractional rate of metabolism of a drug after different routes of administration for renally and hepatically cleared drugs and metabolites

Abstract

A model comprised of four compartments, a central and liver compartment for a drug, and a central and liver compartment for a metabolite, is presented to describe the interrelationships between the area under the curve of the metabolite and physiological parameters after intravenous and intraportal administration of the drug. The model includes renal and hepatic eliminatory mechanisms for both drug and metabolite as long as the metabolite is formed only by the liver. It is found that when competing renal eliminatory pathways exist for a drug, the area under the curve for the metabolite will change according to the route of drug administration. Also, the fractional rate of metabolism of a drug to form the metabolite will be underestimated by the normal use of the ratio areas under the curve of the metabolite. Other properties of the model are also discussed.