Drug interaction of donepezil combined with moxifloxacin
10.12007/j.issn.0258-4646.2025.06.007
- VernacularTitle:多奈哌齐与莫西沙星联合用药的药物相互作用
- Author:
Xuemei SUN
1
;
Zhenying ZHAO
;
Yuxi WANG
;
Peipei CHEN
;
Zixuan LI
;
Min ZHANG
;
Fei YU
Author Information
1. 南开大学第一附属医院,天津市人民医院药学部,天津 300121
- Publication Type:Journal Article
- Keywords:
donepezil;
moxifloxacin;
drug combination;
drug interaction
- From:
Journal of China Medical University
2025;54(6):517-522
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the drug-drug interaction between donepezil hydrochloride and moxifloxacin hydrochloride during combined administration through in vitro liver microsomal metabolism and changes in pharmacokinetic characteristics in rats.Methods A rat liver microsomal incubation system was constructed and optimized.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis of donepezil hydrochloride and high-performance liquid chromatography(HPLC)analysis of moxifloxacin hydro-chloride were performed.The pharmacokinetic and metabolic characteristics of the two drugs,alone and in combination,were compared in vitro using rat liver microsomes and in vivo using rats.Results In the liver microsomal system,the half-life(T1/2)of donepezil hydro-chloride in the combined administration 1 group was prolonged by 29.892％(P＜0.01)and the intrinsic clearance(CLint)was reduced by 23.194％(P＜0.01)compared with the donepezil hydrochloride group.Conversely,the metabolic parameters of moxifloxacin hydrochlo-ride in the combined administration 2 group did not differ significantly from that of the moxifloxacin hydrochloride group(P＞0.05).In the in vivo study,the AUC0～t and AUC0～∞ of donepezil hydrochloride in the combined administration 1 group increased by 44.259％and 44.496％,respectively,maximum plasma concentration(Cmax)increased by 117.723％,T1/2 was prolonged by 98.063％,and CLint was reduced by 35.293％,compared with that in the donepezil hydrochloride group.Moreover,the differences were all statistically significant(P＜0.05).The in vivo study findings were consistent with the results of the in vitro study.Conclusion A drug-drug interaction occurs when moxifloxacin hydrochloride is used in combination with donepezil hydrochloride.Moxifloxacin hydrochloride promotes the absorption of donepezil hydrochloride,inhibits its metabolism,slows its CLint,and increases donepezil exposure in the body.
