色谱法
药代动力学
化学
串联质谱法
液相色谱-质谱法
质谱法
胶囊
药理学
生物
植物
作者
Junfeng Zhu,Like Zhong,Yu Song,Haiying Ding,Wenjuan Xin,Gaoqi Xu,Luo Fang
标识
DOI:10.1002/jssc.202300923
摘要
Regorafenib is a small‐molecule tyrosine kinase inhibitor with severe hepatotoxicity. It undergoes metabolism mainly by CYP3A4 to generate active metabolites regorafenib‐ N ‐oxide (M2) and N ‐desmethyl‐regorafenib‐ N ‐oxide (M5). Wuzhi capsule (WZC) is an herbal preparation derived from Schisandra sphenanthera and is potentially used to prevent regorafenib‐induced hepatotoxicity. This study aims to explore the effect of WZC on the pharmacokinetics of regorafenib in rats. An efficient and sensitive liquid chromatography‐tandem mass spectrometry method was developed to quantitatively determine regorafenib and its main metabolites in rat plasma. The proposed method was applied to the pharmacokinetic study of regorafenib in rats, with or without WZC. Coadministration of regorafenib with WZC resulted in a prolonged mean residence time (MRT) of the parent drug but had no statistically significant difference in other pharmacokinetic parameters. While for the main metabolites of regorafenib, WZC decreased the area under the curve and maximum concentration (C max ), delayed the time to reach C max , and prolonged the MRT of M2 and M5. These results indicate that WZC delayed and inhibited the metabolism of regorafenib to M2 and M5 by suppressing CYP3A4. Our study provides implications for the rational use of the WZC‐regorafenib combination in clinical practice.
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