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Effects of Animal Strain, Dose, and Cotreatment with Saikosaponin b2 on the Pharmacokinetics of Saikosaponin a in Rats.

Abstract

BACKGROUND AND OBJECTIVES

Radix Bupleuri (RB, Chaihu in Chinese) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Saikosaponin a (SSa), the most abundant saikosaponin in RB, exhibits various pharmacological activities, including anti-inflammatory, antitumor, antiviral, immunoregulatory, neuromodulatory, and hepatoprotective activities. A comprehensive study of the pharmacokinetic characteristics of SSa is needed to gain a detailed understanding of its pharmacodynamic mechanism.

METHODS

Here, we determined the effects of rat strain (Sprague Dawley and Wistar), oral dose, and cotreatment with saikosaponin b2 (SSb2) on the pharmacokinetics of SSa by measuring SSa in plasma via LC-MS/MS.

RESULTS

The results showed that the absorption of SSa in Wistar rats was statistically superior to its absorption in Sprague Dawley rats based on pharmacokinetic parameters such as the area under the concentration-time curve (AUC0-t) and the peak concentration (Cmax). Pharmacokinetic studies of different doses of SSa in Wistar rats revealed that the systemic exposure of SSa, based on AUC values, increased disproportionately with dose, indicating that SSa exhibits non-dose-proportional pharmacokinetics. In addition, our studies showed that SSb2, a characteristic component of vinegar-baked Radix Bupleuri (VBRB), inhibits the absorption of SSa in rats.

CONCLUSIONS

The pharmacokinetic data for SSa obtained in this study will play an important role in attempts to better understand the fate of SSa in rats and to explore how these saikosaponins are likely to exert their pharmacological effects in vivo. In addition, further research is needed to elucidate the interactions of saikosaponins with metabolic enzymes and transporters in order to account for the phenomena observed in this study.

Authors+Show Affiliations

Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Educational, 24 Tongjia Lane, Nanjing, 210009, China. State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, 210009, China.Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Educational, 24 Tongjia Lane, Nanjing, 210009, China. State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, 210009, China.Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Educational, 24 Tongjia Lane, Nanjing, 210009, China. State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, 210009, China.Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Educational, 24 Tongjia Lane, Nanjing, 210009, China. State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, 210009, China.Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Educational, 24 Tongjia Lane, Nanjing, 210009, China. songrui_cpu@163.com. State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, 210009, China. songrui_cpu@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31317503

Citation

Fu, Ruijia, et al. "Effects of Animal Strain, Dose, and Cotreatment With Saikosaponin B2 On the Pharmacokinetics of Saikosaponin a in Rats." European Journal of Drug Metabolism and Pharmacokinetics, 2019.
Fu R, Liu J, Xue Y, et al. Effects of Animal Strain, Dose, and Cotreatment with Saikosaponin b2 on the Pharmacokinetics of Saikosaponin a in Rats. Eur J Drug Metab Pharmacokinet. 2019.
Fu, R., Liu, J., Xue, Y., Zhang, Z., & Song, R. (2019). Effects of Animal Strain, Dose, and Cotreatment with Saikosaponin b2 on the Pharmacokinetics of Saikosaponin a in Rats. European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-019-00569-5.
Fu R, et al. Effects of Animal Strain, Dose, and Cotreatment With Saikosaponin B2 On the Pharmacokinetics of Saikosaponin a in Rats. Eur J Drug Metab Pharmacokinet. 2019 Jul 17; PubMed PMID: 31317503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of Animal Strain, Dose, and Cotreatment with Saikosaponin b2 on the Pharmacokinetics of Saikosaponin a in Rats. AU - Fu,Ruijia, AU - Liu,Jingjing, AU - Xue,Yunwen, AU - Zhang,Zunjian, AU - Song,Rui, Y1 - 2019/07/17/ PY - 2019/7/19/entrez JF - European journal of drug metabolism and pharmacokinetics JO - Eur J Drug Metab Pharmacokinet N2 - BACKGROUND AND OBJECTIVES: Radix Bupleuri (RB, Chaihu in Chinese) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Saikosaponin a (SSa), the most abundant saikosaponin in RB, exhibits various pharmacological activities, including anti-inflammatory, antitumor, antiviral, immunoregulatory, neuromodulatory, and hepatoprotective activities. A comprehensive study of the pharmacokinetic characteristics of SSa is needed to gain a detailed understanding of its pharmacodynamic mechanism. METHODS: Here, we determined the effects of rat strain (Sprague Dawley and Wistar), oral dose, and cotreatment with saikosaponin b2 (SSb2) on the pharmacokinetics of SSa by measuring SSa in plasma via LC-MS/MS. RESULTS: The results showed that the absorption of SSa in Wistar rats was statistically superior to its absorption in Sprague Dawley rats based on pharmacokinetic parameters such as the area under the concentration-time curve (AUC0-t) and the peak concentration (Cmax). Pharmacokinetic studies of different doses of SSa in Wistar rats revealed that the systemic exposure of SSa, based on AUC values, increased disproportionately with dose, indicating that SSa exhibits non-dose-proportional pharmacokinetics. In addition, our studies showed that SSb2, a characteristic component of vinegar-baked Radix Bupleuri (VBRB), inhibits the absorption of SSa in rats. CONCLUSIONS: The pharmacokinetic data for SSa obtained in this study will play an important role in attempts to better understand the fate of SSa in rats and to explore how these saikosaponins are likely to exert their pharmacological effects in vivo. In addition, further research is needed to elucidate the interactions of saikosaponins with metabolic enzymes and transporters in order to account for the phenomena observed in this study. SN - 2107-0180 UR - https://www.unboundmedicine.com/medline/citation/31317503/Effects_of_Animal_Strain,_Dose,_and_Cotreatment_with_Saikosaponin_b2_on_the_Pharmacokinetics_of_Saikosaponin_a_in_Rats L2 - https://dx.doi.org/10.1007/s13318-019-00569-5 DB - PRIME DP - Unbound Medicine ER -