Evaluation of Hepatic Metabolism of Salicylic Acid in Perfused Rat Liver

Hepatic metabolism of salicylic acid was studied using a single-pass liver perfusion technique. Livers obtained from male, Sprague-Dawley rats (200–300 g) were perfused with Krebs-Henseleit bicarbonate buffer containing the drug (50–100 μg/mL) and glycine (0.5 or 5 mM) or glucose (5.5 mM) or bovine serum albumin (0.33%). Effluent samples over a 30–50 min interval were analyzed for salicylic acid and its metabolites (gentisic acid, salicyluric acid, and salicyl acyl and salicyl phenolic glucuronides). Effluent concentrations of salicylic acid did not differ from those in the perfusate, indicating that the liver is not a site for the metabolism of this drug. Hepatic uptake studies are needed to confirm this finding.