Elimination of allopurinol by the perfused rat liver preparation

The elimination of allopurinol was studied in the perfused rat liver preparation. When tracer input [14C]-allopurinol concentrations (0.04 to 0.17 microgram/ml) were delivered under constant flow rate (10 ml/min/liver) only once through the rat liver, the steady-state hepatic extraction ratios were high (0.87 +/- 0.03). But at higher input allopurinol concentrations (3.3 to 17 micrograms/ml), concentration-dependent elimination of allopurinol was observed. The steady-state hepatic extraction ratio was drastically reduced with increases in input concentrations. At very high input concentrations of allopurinol (17 micrograms/ml) the hepatic extraction ratio was virtually zero. These findings inferred that the rat liver may play only a moderate role in the elimination of allopurinol in the intact animal.