EFFECT OF PORTAL-VEIN LIGATION AND SILYMARIN TREATMENT ON ASPIRIN METABOLISM AND DISPOSITION IN RATS

The influence of portal hypertension on the metabolism and pharmacokin etics of aspirin was evaluated after the administration of a single or al dose of acetylsalicylic acid (20 mg kg(-1)) in portal-vein-ligated (PVL) rats. Experiments were also performed in control (sham-operated rats) and in rats that received an oral daily dose (150 mg kg(-1)) of silymarin from the tenth day after surgery for 7 d. Plasma concentrati on profiles of all groups exhibited monoexponential decay but with imp ortant changes in pharmacokinetic parameters. The aspirin elimination constant (k) for PVL rats was lower than for control rats, whereas the plasma half-life and area under the curve were greater than those in the control group. However, C-max was comparable with that of the cont rol rats. Urinary excretion of the metabolites (salicylic acid and glu curonides) was significantly altered in PVL rats: the urinary glucuron ides were reduced and urinary salicylic acid was increased. The activi ties of plasma and liver esterases were increased significantly in PVL rats, while the activity of p-nitroanisole-O-demethylase was not affe cted. Depletion of cytochrome P 450 was also noted in the same group o f rats. Silymarin markedly reversed the alterations found in the PVL g roup.