Dataset Information

In Vitro Metabolism of Donepezil in Liver Microsomes Using Non-Targeted Metabolomics.

ABSTRACT: Donepezil is a reversible acetylcholinesterase inhibitor that is currently the most commonly prescribed drug for the treatment of Alzheimer's disease. In general, donepezil is known as a safe and well-tolerated drug, and it was not associated with liver abnormalities in several clinical trials. However, rare cases of drug-related liver toxicity have been reported since it has become commercially available. Few studies have investigated the metabolic profile of donepezil, and the mechanism of liver damage caused by donepezil has not been elucidated. In this study, the in vitro metabolism of donepezil was investigated using liquid chromatography-tandem mass spectrometry based on a non-targeted metabolomics approach. To identify metabolites, the data were subjected to multivariate data analysis and molecular networking. A total of 21 donepezil metabolites (17 in human liver microsomes, 21 in mice liver microsomes, and 17 in rat liver microsomes) were detected including 14 newly identified metabolites. One potential reactive metabolite was identified in rat liver microsomal incubation samples. Metabolites were formed through four major metabolic pathways: (1) O-demethylation, (2) hydroxylation, (3) N-oxidation, and (4) N-debenzylation. This study indicates that a non-targeted metabolomics approach combined with molecular networking is a reliable tool to identify and detect unknown drug metabolites.

SUBMITTER: Kim SE

PROVIDER: S-EPMC8309179 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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In Vitro Metabolism of Donepezil in Liver Microsomes Using Non-Targeted Metabolomics.

Kim Sin-Eun SE Seo Hyung-Ju HJ Jeong Yeojin Y Lee Gyung-Min GM Ji Seung-Bae SB Park So-Young SY Wu Zhexue Z Lee Sangkyu S Kim Sunghwan S Liu Kwang-Hyeon KH

Pharmaceutics 20210623 7

Donepezil is a reversible acetylcholinesterase inhibitor that is currently the most commonly prescribed drug for the treatment of Alzheimer's disease. In general, donepezil is known as a safe and well-tolerated drug, and it was not associated with liver abnormalities in several clinical trials. However, rare cases of drug-related liver toxicity have been reported since it has become commercially available. Few studies have investigated the metabolic profile of donepezil, and the mechanism of liv ...[more]

PMID: 34201744

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Dataset Information

In Vitro Metabolism of Donepezil in Liver Microsomes Using Non-Targeted Metabolomics.

Publications

In Vitro Metabolism of Donepezil in Liver Microsomes Using Non-Targeted Metabolomics.

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