Zhao Ying-Yong, Su Qi, Cheng Xian-Long, Tan Xiao-Jie, Bai Xu, Lin Rui-Chao
Department of Traditional Chinese Medicine, The College of Life Sciences, Northwest University, Xi'an, Shaanxi, PR China.
Bioanalysis. 2012 Mar;4(6):713-23. doi: 10.4155/bio.12.24.
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.
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.
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.
土大黄苷（来源于大黄属植物）具有多种药理活性，包括抗肿瘤、抗血栓形成和抗氧化作用。然而，尚无关于静脉给药后土大黄苷的药代动力学、生物利用度和代谢的相关信息。
建立了超高效液相色谱-四极杆飞行时间质谱联用（UHPLC-Q-TOF/MS）和超高效液相色谱-多级串联质谱联用（UHPLC-多级串联MS）方法，用于研究大鼠体内土大黄苷的药代动力学、生物利用度和代谢情况。通过UHPLC-多级串联MS确认了土大黄苷的代谢产物土大黄素，它是一种细胞色素P450的强效抑制剂。采用UHPLC-Q-TOF/MS测定了土大黄苷和土大黄素的血浆浓度曲线。结果表明，土大黄苷在大鼠血浆中迅速分布并消除。计算出土大黄苷的绝对口服生物利用度为0.03%。静脉给药后土大黄素的血浆浓度迅速升高并逐渐消除。
目前关于土大黄苷的药代动力学、生物利用度和代谢研究将为开发合适的剂型以及合理给药的临床参考提供有用信息。
