Lymphatic absorption of quercetin and rutin in rat and their pharmacokinetics in systemic plasma

Substances and macromolecules absorbed by the lymphatic system avoid hepatic first-pass effect and directly enter the blood circulation system. In this study, an anesthetized, mesenteric lymphatic/duodenum-cannulated rat model was used to investigate the role of lymphatic absorption with intraduodenally administered drugs. Quercetin and rutin were administered, respectively, at dosages of 30 and 300 mg/kg intraduodenally. Lymph and plasma samples were collected every 30 min. These samples were prepared by protein precipitation and then analyzed by high-performance liquid chromatography with a photodiode array detector (HPLC-PDA) and verified by LC tandem mass spectrometry (LC-MS/MS). Quercetin was separated by a C18 reversed-phase column, and rutin was separated by a phenyl reverse-phase column. Pharmacokinetic parameters were calculated using the software WinNonlin Standard Edition Version. The maximum concentration (Cmax) of quercetin recovered in lymph, 1.97+/-0.96 microg/mL, was about 5-fold higher than that in plasma, 0.41+/-0.08 microg/mL. The time to reach the highest concentration (Tmax) of quercetin in lymph was 30 min longer than that in plasma. The maximum concentration (Cmax) of rutin recovered in lymph, 0.86+/-0.13 microg/mL, was slightly lower than that in plasma, 1.35+/-0.37 microg/mL. The area under curve (AUC) of rutin recovered in lymph, 359+/-41 min microg/mL, was about 2-fold higher than the AUC of rutin in plasma, 150+/-22 min microg/mL. This phenomenon was due to the milder concentration decline of rutin in the lymphatic system. These results demonstrate the pharmacokinetic data of lymphatic and systemic absorption after intraduodenally administered quercetin and rutin. It is also the first report revealing the lymphatic absorption of rutin. Although both quercetin and rutin are absorbed and transported mainly via the blood circulation system, the AUC of these two drugs in lymph fluid appeared higher than their respective AUC in plasma.