An-Najah Staff

Hesperetin and naringenin, the aglycones of the flavanone glycosides hesperidin and naringin, ‎occur naturally in citrus fruits. They exert interesting pharmacological properties such as ‎antioxidant, anti-inflammatory, blood lipid and cholesterol lowering and are considered to ‎contribute to health benefits in humans. However, no information is available on the ‎pharmacokinetics of the citrus flavanones hesperetin and naringenin after their oral administration ‎to humans as pure aglycones. Therefore, the objective of the present investigation was the ‎evaluation of the pharmacokinetic parameters of hesperetin and naringenin in plasma and urine, ‎after their single oral administration in humans in the form of solid dispersion capsules, and also to ‎improve the absorption rate of flavanones by using aglycones rather than the naturally occurring ‎glycosides.‎

Six healthy volunteers received orally 135 mg of each compound, hesperetin and naringenin, under ‎fasting conditions. Blood samples were collected at 14 different time points over a 12 h period. ‎Urine was collected over 24 h, in five sequential timed intervals. Plasma and urine hesperetin and ‎naringenin concentrations, after enzymatic hydrolysis of their conjugated forms, were measured ‎using validated high-pressure liquid chromatography methods. Pharmacokinetic parameters for ‎hesperetin and naringenin, such as C(max), T(max), AUC(0-t), AUC(0-infinity), CL/F, V/F, t(1/2), ‎MRT, A(e), A(e)((0-24)), and R(max) were calculated from their plasma or urine concentrations.‎

Pharmacokinetic analysis showed that both hesperetin and naringenin were rapidly absorbed and ‎their concentrations in plasma observed 20 min after dosing and reached a peak in 4.0 and 3.5 h, ‎respectively. The mean peak plasma concentration (C(max)) for hesperetin and naringenin were ‎‎825.78+/-410.63 ng/ml (2731.8+/-1358.4 nmol/l) and 2009.51+/-770.82 ng/ml (7386.6+/-2833.4 ‎nmol/l), respectively and the mean AUC(0-infinity) values were 4846.20+/-1675.99 ng h/ml and ‎‎9424.52+/-2960.52 ng h/ml for hesperetin and naringenin, respectively. The elimination half-life for ‎hesperetin was found to be 3.05+/-0.91 h and for naringenin 2.31+/-0.40 h, respectively. The mean ‎values of the relative cumulative urinary excretion, as percentage of the administered dose, for ‎hesperetin and naringenin, were found to be 3.26+/-0.44 and 5.81+/-0.81%, respectively.‎

Oral administration of the flavanone aglycones, hesperetin and naringenin, lead to their rapid ‎absorption as their conjugated forms. The cumulative urinary recovery data indicated low ‎bioavailability for both flavanone aglycones, owing to extensive first-pass metabolism partly by ‎cleavage of the C-ring by the enzymes of intestinal bacteria leading to degradation products such ‎as phenolic acids.‎