Comparative pharmacokinetics of naringin and neohesperidin after oral administration of flavonoid glycosides from Aurantii Fructus Immaturus in normal and gastrointestinal motility disorders mice

Abstract

ObjectiveTo compare the pharmacokinetics of naringin and neohesperidin after oral administration of Zhishi total flavonoid glycosides (ZSTFG) extracted from Aurantii Fructus Immaturus in normal and gastrointestinal motility disorders (GMD) mice. MethodsZSTFG was orally given to normal and GMD mice induced by atropine or dopamine. The plasma samples were incubated with β-glucuronidase/sulfatase, the total (free + conjugated) naringenin and hesperitin were extracted with acetonitrile. The validated HPLC-MS/MS method was successfully applied to the pharmacokinetic study. ResultsThe results showed that, compared with the normal group, AUC0–∞, AUC0–t and Cmax for total naringenin and hesperitin were significantly higher (P < 0.01 or P < 0.05), while CLZ/F for total naringenin and hesperitin was significantly lower (P < 0.01) in the GMD group. Tmax, t1/2z, MRT0-t, and MRT0-∞ for naringenin were longer (P < 0.01) in the GMD group than those in the normal group. ConclusionThe results showed that there were significant differences in pharmacokinetic parameters of naringenin and hesperitin between normal and GMD groups. It was suggested that the absorption of naringenin and hesperitin was increased, and the elimination processes of naringenin and hesperitin were slower in the GMD group than the normal group. The data are of value for further pharmacological studies of ZSTFG and would be useful to provide a reference for improving the therapeutic regimen of ZSTFG in clinical trials.