Chronic quercetin feeding decreases plasma concentrations of salicylamide phase II metabolites in pigs following oral administration

Abstract

1. We investigated acute effects and effects after chronic intake of the orally administered flavonol quercetin on pharmacokinetics of salicylamide metabolites (SAM) after oral administration of salicylamide in pigs.

2. Salicylamide (8 mg/kg body weight) was orally administered to seven pigs either without or with quercetin (10 mg/kg body weight). Additionally, salicylamide was administered to five pigs that had received a diet supplemented with the flavonol for 1 week. Daily quercetin intake was 10 mg/kg in these animals.

3. Co-ingestion of quercetin with the drug did not alter area under the concentration-time curve (AUC_0→∞), time to achieve maximum plasma concentration (t_max), mean residence time (MRT) or half-life (t_1/2) of SAM. However, maximum plasma concentration (c_max) of SAM was lower when quercetin was administered concomitantly.

4. After quercetin pre-treatment for 1 week AUC_0→∞, t_1/2 and MRT of SAM were decreased, while other parameters investigated were not affected.

5. Co-ingestions and dietary pre-treatment with quercetin influenced SAM metabolism after oral salicylamide intake. But effects seen after acute concomitant intake are rather explained by induced salicylamide excretion from the intestinal mucosa, whereas quercetin pre-treatment seemed to induce hepatic enzymes involved in phase-II metabolism and thereby enhanced elimination of SAM.

Keywords::

• Phase II biotransformation
• enzyme induction
• drug interaction
• polyphenols