Pharmacokinetics and bioavailability of caffeic acid after oral administration in rabbits

The pharmacokinetics and bioavailability of caffeic acid (ca) were studied after oral administration in rabbits. three different doses (5, 10 and 25 mg/kg) of ca solution were orally administered to six rabbits with a one week washout period between each dose. The concentration-time profiles of caffeic acid showed a double peak phenomenon and the elimination phase was obviously different than after intravenous administration, indicating that CA shows 'flip-flop' pharmacokinetics. The pharmacokinetic parameters of the CL(total), CL(r), CL(nr), and absorption phase half-life showed no significant differences for each dose after oral administration. These results indicate that CA exhibits dose-independent pharmacokinetics after oral administration in the dose range of 5 to 25 mg/kg. The results also show that the values of the AUC and C(max) increased linearly with dose in the range of 5 to 25 mg/kg. The absolute bioavailability values of CA were 0.364 ± 0.052, 0.379 ± 0.037 and 0.402 ± 0.087 and the percentages of unchanged CA excreted in the urine were 23.2 ± 4.9, 22.7 ± 3.7 and 22.0 ± 5.3 % for doses of 5, 10 and 25 mg/kg, respectively. There were no significant differences in the absolute bioavailability and percentages of unchanged CA excreted in the urine over this dose range.