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Current Drug Metabolism

Author(s): Qiru Tian, Huan Jin, Xiaokui Huo, Yupu Zhao, Wenhui Wu, Lei Xu, Yinan Wang, Xiaobo Yang, Chengpeng Sun, Sa Deng and Xiaohong Shu*

DOI: 10.2174/1389200224666230510125610

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Comparative Pharmacokinetics of Scoparone and its Metabolite Scopoletin in Normal and ANIT-induced Intrahepatic Cholestatic Rats

Page: [303 - 311] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Scoparone, the principal natural active ingredient of Artemisia capillaries (Yin Chen), can effectively treat cholestatic diseases, but the pharmacokinetic properties of scoparone are rarely studied in intrahepatic cholestatic rats.

Objective: A sensitive and rapid LC-MS/MS method was established to detect scoparone and its metabolite of scopoletin in rat plasma and then compare their plasma pharmacokinetic differences between the normal and ANITinduced cholestasis rats.

Methods: Positive ionization was used to separate scoparone and scopoletin using acetonitrile and 0.1 % formic acid water as the mobile phase on a Hypersil ODS-BP column.

Results: The calibration curves presented good linearity (R=0.9983 and 0.9989) in the concentration range of 10- 10000 ng/mL and 0.5-500 ng/mL for scoparone and scopoletin, respectively. The precision of ≤ 9.4% and the accuracy ranged from -6.4% to 6.8% were recorded over three validation runs, and the recovery was higher than 83.9%. Under different storage conditions, scoparone and scopoletin were stable. Therefore, we studied the pharmacokinetic properties of scoparone and scopoletin in rats after a single oral administration with the above method. According to the results, the pharmacokinetic parameters of AUC, t1/2, and Cmax values of scoparone in the ANIT group were increased by 106%, 75%, and 44%, respectively, while these values of scopoletin were increased by 142%, 62%, and 65%.

Conclusion: The findings indicated that the pharmacokinetic properties of scoparone and scopoletin were significantly different between the normal and ANIT-induced cholestasis rats, which suggested that the clinical application dosage of scoparone should be adjusted according to the liver function of patients.

Graphical Abstract

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