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

✍ Scribed by LILIANA FAVARI; CLAUDIA SOTO; MARISABEL MOURELLE

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 423 KB
• Volume: 18
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199701)18:1<53::aid-bdd3>3.0.co;2-9

✦ Synopsis

The in¯uence of portal hypertension on the metabolism and pharmacokinetics of aspirin was evaluated after the administration of a single oral dose of acetylsalicylic acid (20 mg kg 71 ) 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 71 ) of silymarin from the tenth day after surgery for 7 d. Plasma concentration pro®les of all groups exhibited monoexponential decay but with important 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 control rats. Urinary excretion of the metabolites (salicylic acid and glucuronides) was signi®cantly altered in PVL rats: the urinary glucuronides were reduced and urinary salicylic acid was increased. The activities of plasma and liver esterases were increased signi®cantly in PVL rats, while the activity of p-nitroanisole-O-demethylase was not aected. Depletion of cytochrome P 450 was also noted in the same group of rats. Silymarin markedly reversed the alterations found in the PVL group.