Pharmacokinetic study of paeoniflorin in mice after oral administration of Paeoniae radix extract

Abstract

Quantification of paeoniflorin, the principal bioactive component of Paeoniae radix, in mice plasma following oral administration of Paeoniae radix extract was achieved by using a simple and rapid high-performance liquid chromatographic method. The calibration curve for paeoniflorin was linear (r²=0.998) over the concentration range 10–200 ng/ml. The coefficients of variation of intra- and inter-day assays were 15.04, 7.31, 6.14, 6.55, 6.63% and 12.71, 6.07, 3.61, 5.51, 4.52% at concentrations of 10, 60, 100, 160, 200 ng/ml, respectively. The recoveries of paeoniflorin from mice plasma were found to be 74.49, 76.83, 80.38 and 80.56% for concentrations of 30, 80, 120 and 160 ng/ml, respectively. The plasma concentration–time curves were fitted with mean terminal half-lives (t_1/2) of 94.16 min.

Introduction

Paeoniae alba radix (White Paeony Root; Baishao), the dried peeled root of Paeonia lactiflora Pall. (family Paeoniaceae), is one of the Chinese traditional tonic crude drugs. It has been used as a spasmolytic and pain-relieving agent and has long been used to regulate the menstrual flow, for the treatment of menstrual disorders and to relieve abdominal spasmodic pain and muscle stiffness. Paeoniflorin (structure shown in Fig. 1), a water-soluble substance isolated from the root of P. lactiflora in 1963 [1], is one of the bioactive components in Paeoniae radix and has been reported to exhibit anticoagulant [2], neuromuscular blocking [3], [4], [5], [6], [7], [8], [9], [10], cognition-enhancing [11], [12], [13], [14], [15], immunoregulating [16] and antihyperglycemic effects [17]. Because knowledge of the pharmacokinetic processes can help us to explain and predict a variety of events related to the efficacy and toxicity of herbal preparations, it is important to investigate the pharmacokinetics of paeoniflorin for further evaluation of its clinical applications.

Although paeoniflorin has been demonstrated to exhibit neuromuscular blocking and cognition-enhancing effects, there are no appropriate pharmacokinetic data to support an ideal dosing regimen for these clinical applications at this stage. From a pharmacokinetic point of view, to determine a rational dosing interval (e.g., tid or qid regimen), the half-life (t_1/2) of paeoniflorin should be considered first. In addition the time to reach maximum concentration (t_max) is required for the estimation of onset of pharmacological response. Therefore, the pharmacokinetics of paeoniflorin are useful for providing an ideal dosing regimen and enhancing the safety and efficacy of paeoniflorin in clinical applications.

Because most Chinese medicines are administered orally as extract powders, decoctions or extract granules in clinical use, the pharmacokinetics after administration of purified paeoniflorin reported in recent years [18], [19], [20] could not used as a suitable reference in clinical application. To obtain the available pharmacokinetic data of paeoniflorin, a simple and rapid high-performance liquid chromatographic (HPLC) method was developed to determinate paeoniflorin in mice plasma after oral administration of Paeoniae radix extract. The present study describes the absorption and excretion of paeoniflorin; the related pharmacokinetic profiles of paeoniflorin are evaluated and discussed.