Quantitative determination of organ contribution to excretory metabolism

A method for the quantitative determination of organ contribution to in vivo excretory metabolism is described. By excretory metabolism, we mean metabolism of a compound by an organ with direct excretion. The technique separately and simultaneously quantifies clearance of circulating metabolite and clearance of circulating precursor by excretory metabolism. For xenobiotics, the method involves the simultaneous infusion of radiolabeled precursor and unlabeled metabolite. The method is dependent upon the achievement of steady-state plasma concentrations of precursor and metabolite and on the ability to accurately analyze, both chemically and radioactively, the precursor in plasma, and the metabolite in both plasma and excretory fluid. The technique is not compromised by in vivo conversion of metabolite to precursor. This method is suitable for the simultaneous quantitative determination of the contribution of several organs to the formation of any number of metabolites present in excretory fluids. The simultaneous contribution of excretory metabolism to the urinary and biliary elimination of 1-naphthol in the rat is presented.