Effects of cerebral ischemia-reperfusion on pharmacokinetic fate of paeoniflorin after intravenous administration of Paeoniae Radix extract in rats

The objective of the present study was to investigate the effects of cerebral ischemia-reperfusion on pharmacokinetics of paeoniflorin after intravenous administration of Paeoniae Radix extract (PRE) in rats. The cerebral ischemia-reperfusion rats were induced by occluding the bilateral carotid arteries of normal rats for 2 h, followed by reperfusion. The resultant animals were immediately administrated by PRE (at a dose of 60 mg/kg of paeoniflorin) via the femoral vein, whilst the same dose was injected to the normal rats. Plasma samples were collected at different time to construct pharmacokinetic profiles by plotting drug concentration versus time. Quantification of paeoniflorin in rat plasma was achieved by using a simple and rapid high-performance liquid chromatographic method. In normal rats, the major parameters of distribution half-life (t(1/2alpha)), elimination half-life (t(1/2beta)), area under the plasma concentration-time (AUC), mean retention time (MRT), and clearance (CL), estimated by an open two-compartmental model, were 0.69, 18.77 min, 5338.71 (mu gmin)/ml, 18.13 min and 0.0162 mg/(kg min), respectively. However. in ischemia-reperfusion rats, the corresponding parameters were 2.04, 24.51 min, 9626.00 (mug min)/ml, 29.75 min and 0.0071 mg/(kg min), respectively. The results showed that ischemia-reperfusion significantly increased AUC values, decreased CL values, and prolonged the terminal half-life of paeoniflorin. These findings suggest that the injuries of ischemia-reperfusion could play an important role in pharmacokinetic process of paeoniflorin. (C) 2004 Elsevier Ireland Ltd. All rights reserved.