Distribution of antipyrine in the rat liver

The rate and extent of hepatic distribution of antipyrine was examined in the rat isolated perfused liver. Tritiated water and [14C]antipyrine were injected simultaneously into the portal vein as a bolus using either Krebs-Ringer bicarbonate or rat plasma as the perfusate. The effluent profiles of each compound using the two perfusates were superimposable, a finding expected for water and consistent for antipyrine, which was negligibly bound in rat plasma. Although full recovery (97%) of administered material was achieved with both compounds, the fractional output profile for antipyrine peaked at a lower value (0.10 mL-1) and at a later time (24 s) than water (0.14 mL-1, 17.5 s), due to antipyrine having a larger volume of distribution (water 0.61 mL (g liver) -1); antipyrine 0.81 mL (g liver)-1). This observation is explained by antipyrine binding to, or partitioning into cellular components. Nonetheless, like water, distribution of antipyrine into hepatic cells is perfusion rate limited as evidenced by the superimposition of the dimensionless plots of fractional output vs time normalized to mean residence time.