Effect of portal vein ligation and silymarin treatment on aspirin metabolism and disposition in rats.
The influence of portal hypertension on the metabolism and pharmacokinetics of aspirin was evaluated after the administration of a single oral dose of acetylsalicylic acid (20 mgkg(-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 mgkg(-1)) of silymarin from the tenth day after surgery for 7 d. Plasma concentration profiles 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, Cmax was comparable with that of the control rats. Urinary excretion of the metabolites (salicylic acid and glucuronides) was significantly altered in PVL rats: the urinary glucuronides were reduced and urinary salicylic acid was increased. The activities of plasma and liver esterases were increased significantly in PVL rats, while the activity of p-nitroanisole-O-demethylase was not affected. Depletion of cytochrome P 450 was also noted in the same group of rats. Silymarin markedly reversed the alterations found in the PVL group.
Favari
L
L
Departamento de Farmacologia y Toxicologia, Cinvestav-I.P.N., Mexico.
Soto
C
C
Mourelle
M
M
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001241:Aspirin / Q000378:metabolism* / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006207:Half-Life; D006975:Hypertension, Portal / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012838:Silymarin; D003577:Cytochrome P-450 Enzyme System; D001241:Aspirin