Pharmacokinetics of Paradol Analogues Orally Administered to Rats

The kinetics parameters of paradols with different acyl chain lengths have been evaluated to determine their antiobesity site of action. Rats were orally administered olive oil containing 0-, 6-, 8-, or 12-paradol, and blood samples were collected at different time points. The concentrations of the paradols in the plasma were analyzed both with and without β-glucuronidase treatment. The area under the plasma concentration-time curve from 0 to 24 h (AUC(0-24h)) of the parent compounds decreased with increasing acyl chain length. Whereas 12-paradol showed the largest AUC(0-24h) with the longest time to reach its maximum plasma concentration of all of the compounds tested, the AUC(0-24h) values of the metabolites decreased with increasing acyl chain length. These results indicate that increasing acyl chain length leads to a decrease in the absorption of paradols via the intestinal tract, the wall of which was estimated to be their antiobesity site of action.