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

Abstract

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.

Keywords:

• Absorption
• bioavailability
• paeoniflorin
• paeoniflorin-6'O-benzene sulfonate
• pharmacokinetics

Acknowledgements

The authors would like thank Prof. Jin-qi Liu (Anhui University of Chinese Medicine), Prof. Yu-hua Sheng (Anhui University), Dr. Qing-bo Yu (Anhui University) and Dr. An Zhou (Anhui University of Chinese Medicine) for their excellent technical assistance.

Declaration of interest

The authors declare that they have no conflict of interest. This work was financially supported by the National Natural Science Foundation of China (No.81330081, No.81302845, and No.81473223), the Training Program of Academic and Technical Leaders in the Universities of Anhui Province (No. 34), the Anhui Province Nature Science Foundation in the University (No. KJ2013A158) and the Grants for Scientific Research of BSKY (No.XJ201211) from Anhui Medical University.

Supplementary material available online