Study and exploration of the pharmacokinetics of traditional Tibetan medicine Ruyi Zhenbao tablets after single and long-term administration

Hongping Hou; Tengfei Chen; Ziying Xu; Zihui Yu; Caixia Wang; Rongxia Liu; Bo Peng; Wei Yang; Feng Li; Xiangyi Che; Bing Li; Yu Wang; Ling Song; Yunhang Gao; Zuguang Ye; Guangping Zhang

doi:10.3389/fphar.2022.948693

Study and exploration of the pharmacokinetics of traditional Tibetan medicine Ruyi Zhenbao tablets after single and long-term administration

Front Pharmacol. 2022 Sep 29:13:948693. doi: 10.3389/fphar.2022.948693. eCollection 2022.

Authors

Hongping Hou¹, Tengfei Chen¹, Ziying Xu², Zihui Yu², Caixia Wang¹, Rongxia Liu³, Bo Peng¹, Wei Yang¹, Feng Li⁴, Xiangyi Che⁴, Bing Li⁵, Yu Wang⁵, Ling Song¹, Yunhang Gao¹, Zuguang Ye¹, Guangping Zhang¹

Affiliations

¹ Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
² Capital Institute of Pediatrics, Beijing, China.
³ School of Pharmacy, Yantai University, Yantai, China.
⁴ Gansu Cheezheng Tibetan Medicine Co., Ltd., Beijing, China.
⁵ Yantai Saipute Analyzing Service Co., Ltd., Yantai, China.

Abstract

Tibetan medicine is one of the oldest traditional medicine systems in the world. Taking the Ruyi Zhenbao tablet (RYZB) as an example, which is a widely used classic oral Tibetan medicine, this article discusses the pharmacokinetics of single administration and long-term treatment and analyzed its metabolic properties and tissue distribution in vivo. After single administration, blood samples were collected before administration and at different time points after administration in different groups of rats. In the study of long-term treatment effects, blood samples were collected from the animals in each group on days 1, 15, and 30 and on day 15 after withdrawal. The results showed that after a single administration, the dose change had no significant effect on the T_1/2 and T_max of agarotetrol, isoliquiritigenin, and piperine (p > 0.05). There was a certain correlation between the increase in AUC_0-t and the C_max of agarotetrol, isoliquiritigenin, piperine, and the increase in dosage, with a dose range of 0.225-0.900 g/kg. There were no significant differences in C_max and AUC_0-t of ferulic acid at different doses (p > 0.05). Meanwhile, there was no significant sex-based difference in the pharmacokinetic parameters of these four components in rats. After long-term administration, the distribution agarotetrol in various tissues of rats was kidney > liver > heart > brain; the tissue distribution in low- and medium-dose groups of isoliquiritigenin was liver > kidney > heart > brain, and in the high-dose group, kidney > liver > heart > brain. The tissue distribution of piperine in each dose group was liver > kidney > heart > brain, and that of ferulic acid in each dose group was kidney > liver > heart > brain. Through the establishment of the previously developed methodology, the pharmacokinetic properties of RYZB were analyzed after a single administration and long-term administration. Our findings confirmed this approach for the exploration and establishment of a pharmacokinetic evaluation of Tibetan medicine, to support its guiding role in clinical application, but also to accelerate research into Tibetan medicine theory and medicine and to provide a solid foundation for the translation of Tibetan medicine throughout the world.

Keywords: Ruyi Zhenbao tablet; Tibetan medicine; long-term administration; pharmacokinetics; single administration.