Effect of inflammation and proadifen on the disposition of antipyrine, lignocaine and propranolol in rat isolated perfused liver.

The effect of inflammation, induced in rats by injection of turpentine oil, on drug disposition has been evaluated in rat isolated perfused livers. The drugs studied were a low extraction drug, antipyrine, and two high extraction drugs, lignocaine and propranolol. Turpentine significantly increased the half-life of antipyrine and of propranolol, but not that of lignocaine. Proadifen (SKF 525A) significantly increased the half-life of all three drugs. Turpentine decreased the clearance of antipyrine significantly by about 50% and that of propranolol non-significantly by about 20%, but did not affect the clearance of lignocaine. Proadifen significantly decreased the clearance of all three drugs, but this was most pronounced for antipyrine. In both turpentine- and proadifen-treated rats a significant increase in volume of distribution of propranolol was observed. The results show that, as with proadifen, turpentine-induced inflammation affects the hepatic clearance of antipyrine in the rat isolated perfused liver. With both high extraction drugs, the effect of inflammation on their clearance was low or absent, in contrast to the effect of proadifen. This suggests that a possible effect of inflammation on intrinsic clearance is not large enough to influence the hepatic clearance of the high extraction drugs.