Comparative Pharmacokinetic Studies of Paeoniflorin, Albiflorin and Oxypaeoniflorin Between Normal and Cerebral Ischemia
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ORIGINAL
Comparative Pharmacokinetic Studies of Paeoniflorin, Albiflorin and Oxypaeoniflorin Between Normal and Cerebral Ischemia–Reperfusion Rats Based on the Simultaneous Determinations Using an UPLC‑MS–MS Method Lijun Zhu1 · Shanshan Sun1 · Xin Li1 · Yanxi Hu1 · Yancheng Li2 · Yufeng Liu1,3 Received: 3 June 2020 / Revised: 8 August 2020 / Accepted: 1 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract To explore the pharmacokinetic characteristics of the three monoterpene glycosides (paeoniflorin, albiflorin and oxypaeoniflorin) extracted from the Radix Paeoniae Rubra (RPR), we determined the plasma concentrations of these components in the cerebral ischemia–reperfusion (CIR) rats and the normal rats by a self-developed and validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS–MS) method. In this study, the CIR rats and the normal rats both underwent an intravenous administration of total paeony glucosides (TPG). The blood samples were collected from rats by eye puncture at a series of time points. Then, the pharmacokinetic parameters of the three components were calculated, including the half-life (t1/2), the area under curve of the concentration–time (AUC), the mean residence time (MRT), apparent volume of distribution (Vz) and the clearance (CL). Studies demonstrated that the Vz of albiflorin, the Vz of oxypaeoniflorin, the t1/2 of oxypaeoniflorin and the MRT of oxypaeoniflorin increased in the CIR rats versus the normal rats. Moreover, we found albiflorin and oxypaeoniflorin showed smaller AUC, longer MRT, larger Vz and larger CL than paeoniflorin both in CIR rats and normal rats. In conclusion, we used a validated method to determine the pharmacokinetic characteristics of three monoterpene glycosides in both CIR rats and normal rats simultaneously. These results demonstrated that there were meaningful differences among the pharmacokinetics of the three monoterpene glycosides in TPG either in normal rats or CIR rats. And the CIR model had influences on the in vivo process both of albiflorin and oxypaeoniflorin. Keywords Pharmacokinetic · Paeoniflorin · Albiflorin · Oxypaeoniflorin · Cerebral ischemia–reperfusion
Introduction Ischemic cerebrovascular disease (ICVD) refers to the disorder of supplying blood to the brain based on the lesions of blood vessel wall or the hemodynamic disturbances. It could induce necrosis or emolliate of brain tissues and also cause a series of neurologic deficits [1–4]. Therefore, over the past * Yufeng Liu [email protected] 1
School of Pharmaceutical Sciences, Liaoning University, Shenyang 110036, People’s Republic of China
2
Department of Epidemiology, University of Florida, Gainesville, FL 32608, USA
3
Natural Products Pharmaceutical Engineering Technology Research Center of Liaoning Province, Shenyang 110036, People’s Republic of China
decades, ischemic cerebrovascular diseases have become one of the leading causes of the worldwide health issues, and seriously threaten to the public health [
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