BACKGROUND: Rhaponticin (Rheum L.) demonstrates a variety of pharmacological activities, including antitumor, antithrombotic and antioxidant effect. However, there is no information describing the pharmacokinetics, bioavailability and metabolism of rhaponticin after intravenous administration. RESULTS: UHPLC-Q-TOF/MS and UHPLC-multistage tandem MS methods were developed for the pharmacokinetics, bioavailability and metabolism of rhaponticin in rats. The metabolite of rhaponticin, rhapontigenin, a potent inhibitor of cytochrome P450, was confirmed by UHPLC-multistage tandem MS. The plasma profile of rhaponticin and rhapontigenin was determined by UHPLC-Q-TOF/MS. The results showed that rhaponticin was rapidly distributed and eliminated from rat plasma. The absolute oral bioavailability of rhaponticin was calculated to be 0.03%. The plasma concentrations of rhapontigenin rapidly increased and gradually eliminated after intravenous administration. CONCLUSION: The present pharmacokinetics, bioavailability and metabolism studies of rhaponticin will provide helpful information for development of suitable dosage forms and clinical references on rational administration.
BACKGROUND: Rhaponticin (Rheum L.) demonstrates a variety of pharmacological activities, including antitumor, antithrombotic and antioxidant effect. However, there is no information describing the pharmacokinetics, bioavailability and metabolism of rhaponticin after intravenous administration. RESULTS: UHPLC-Q-TOF/MS and UHPLC-multistage tandem MS methods were developed for the pharmacokinetics, bioavailability and metabolism of rhaponticin in rats. The metabolite of rhaponticin, rhapontigenin, a potent inhibitor of cytochrome P450, was confirmed by UHPLC-multistage tandem MS. The plasma profile of rhaponticin and rhapontigenin was determined by UHPLC-Q-TOF/MS. The results showed that rhaponticin was rapidly distributed and eliminated from rat plasma. The absolute oral bioavailability of rhaponticin was calculated to be 0.03%. The plasma concentrations of rhapontigenin rapidly increased and gradually eliminated after intravenous administration. CONCLUSION: The present pharmacokinetics, bioavailability and metabolism studies of rhaponticin will provide helpful information for development of suitable dosage forms and clinical references on rational administration.
Authors: Mika Reinisalo; Anna Kårlund; Ali Koskela; Kai Kaarniranta; Reijo O Karjalainen Journal: Oxid Med Cell Longev Date: 2015-06-09 Impact factor: 6.543