Pharmacokinetic comparisons of Paeoniflorin and Paeoniflorin-6'O-benzene sulfonate in rats via different routes of administration

1.?The pharmacokinetics study of Paeoniflorin (Pae) and its acylated derivative (CP-25) was performed.

2.?The structure of CP-25 was identified by mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR). The rats were injected with CP-25(6, 12, 24?mg/kg) and orally treated with CP-25 (32, 64, 128?mg/kg), respectively. An high-performance liquid chromatography (HPLC) assay was developed to determine the plasma concentrations of Pae and CP-25.

3.?The results of MS and NMR showed that the acylated product was Pae-6'O-benzene sulfonate (CP-25). The plasma levels in oral CP-25 groups were detectable, whereas those of Pae in the oral groups (25 and 50?mg/kg) were undetectable. More specifically, the C_max values of oral CP-25 were 0.12, 0.19 and 0.44?μg/ml, and the corresponding t_1/2β of CP-25 were 1.44, 2.12 and 2.11?h, respectively. In addition, the t_1/2β values of intravenous CP-25 were 161.99, 152.81 and 153.76?min, respectively.

4.?Compared with the venous pharmacokinetics parameters of Pae, those of the t_1/2β, MRT, Vd and CL/F in the CP-25 groups increased noticeably. As expected, compared with oral parameters of Pae, those of t_1/2a, t_1/2β, AUC, MRT and Vd in the CP-25 group increased obviously. Finally, the absolute bioavailability of Pae and CP-25 were 3.6 and 10.6%, respectively.

5.?Our results indicate that CP-25 is characterized by improved absorption, well distribution, lower clearance, long mean residence time, and moderate bioavailability in rats.