Comparison of metabolic pharmacokinetics of naringin and naringenin in rabbits.

Naringin and naringenin are antioxidant constituents of many Citrus fruits. Naringenin is the aglycone and a metabolite of naringin. In order to characterize and compare the metabolic pharmacokinetics of naringenin and naringin, naringenin was administered intravenously and orally to rabbits, and naringin was administered orally. The concentration of naringenin in serum prior to and after enzymatic hydrolysis was determined by HPLC method. The pharmacokinetic parameters were calculated by using WINNONLIN. The results showed that the absolute bioavailability of oral naringenin was only 4%, whereas after taking the conjugated naringenin into account, it increased to 8%. When naringin was administered orally, only little naringenin and predominantly its glucuronides/sulfates were circulating in the plasma. The ratio of AUC of naringenin conjugates to the total naringenin absorbed into the systemic circulation after oral naringenin was much higher when compared to that after i.v. bolus of naringenin, indicating that extensive glucuronidation/sulfation of naringenin occurred during the first pass at gut wall. Oral dosing of naringin resulted in even higher ratio of AUC of naringenin conjugates to the total naringenin than that after oral naringenin. Our results also showed that there were great differences in pharmacokinetics of naringin and naringenin. Oral naringin resulted in latter Tmax, lower Cmax and longer MRT (mean residence time) for both naringenin and its conjugated metabolites than those after oral naringenin.