1. Identification of the perpetrator imperatorin in Xin-yi-san-theophylline interaction: observed and predicted herb-drug interaction in rats.
- Author
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Wang HJ, Chen AC, Chen HY, Cheng HC, Kao LT, Lu CK, Tsai KC, Lee IJ, and Ueng YF
- Subjects
- Rats, Humans, Animals, Fluvoxamine pharmacology, Bronchodilator Agents pharmacokinetics, Theophylline pharmacokinetics, Herb-Drug Interactions
- Abstract
Objectives: Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats., Methods: The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine., Key Findings: XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3-10 fold. In a dose-dependent manner, XYS and imperatorin (0.1-10 mg/kg) treatments significantly decreased theophylline clearance by 27-33% and 19-56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51-112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27-57%) by XYS was moderate., Conclusions: XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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