Moment analysis of hepatic local disposition of allopurinol and oxipurinol: metabolism kinetics from allopurinol to oxipurinol in the rat isolated perfused liver

Abstract— Drug metabolism in the liver was examined by the rat isolated perfused liver using the single-pass bolus-input technique. The test compounds, allopurinol and its metabolite oxipurinol, were independently introduced into the liver from the portal vein, and the concentration profiles in the venous outflow were monitored and kinetically analysed by moment theory. The recovery ratios of allopurinol and oxipurinol after the individual administration of each drug were estimated to be 0·17 (±0·08 s.d.) and 1·03 (± 0·02 s.d.), respectively. The outflow recovery ratio of oxipurinol as the metabolite after allopurinol administration was estimated to be 0·80 (±0·07 s.d.). These results indicate that the combined outflow recovery of the precursor and the metabolite after allopurinol administration is almost 100% in the rat liver.