Academic Journal
Function of 38 variants CYP2C9 polymorphism on ketamine metabolism in vitro
Title: | Function of 38 variants CYP2C9 polymorphism on ketamine metabolism in vitro |
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Authors: | Xiang Zheng, Ping Fang, Su-su Bao, Dan Lin, Jian-ping Cai, Guo-xin Hu |
Source: | Journal of Pharmacological Sciences, Vol 135, Iss 1, Pp 8-13 (2017) |
Publisher Information: | Elsevier, 2017. |
Publication Year: | 2017 |
Collection: | LCC:Therapeutics. Pharmacology |
Subject Terms: | Ketamine, CYP2C9, Gene polymorphism, Metabolism, Intrinsic clearance, Therapeutics. Pharmacology, RM1-950 |
More Details: | Background: Cytochrome P450 proteins (CYP 450) is the most important enzyme system of drug phase I metabolism in liver. In previous reports, reduced efficiency or increased risk of adverse events can be affected by primary sequence mutation in CYP450. Aim: To investigate the effect of gene polymorphism on the metabolism of ketamine in vitro, including the new alleles: 2C9*58, *59 and *60. Method: Incubation system which was contained insect microsome, b5, NADPH and 1M PBS incubated 10 μM–1000 μM ketamine in 37 °C for 40 min concentration of norketamine was analyzed by ultra-performance liquid chromatography–tandem mass spectrometry system (UPLC-MS/MS). Result: Catalytic activity of thirty-eight CYP2C9 alleles on ketamine metabolism to norketamine was surveyed. Compared with 2C9*1, three alleles (2C9*40, *49 and *51) was demonstrated dramatically increased intrinsic clearance (1.2-fold–3.75-fold); four subtypes (2C9*27, *31, *41 and *56) exhibited no significantly change on enzyme activity. The resting 31 alleles expressed different degrees of reduction compared with wild type. Conclusion: The result of research warns that attention should be more paid on individual who carry on the special 2C9 alleles under the situation of administrating ketamine. |
Document Type: | article |
File Description: | electronic resource |
Language: | English |
ISSN: | 1347-8613 |
Relation: | http://www.sciencedirect.com/science/article/pii/S1347861317301226; https://doaj.org/toc/1347-8613 |
DOI: | 10.1016/j.jphs.2017.08.006 |
Access URL: | https://doaj.org/article/82c779b6f58c4a0595d6b3b83034c196 |
Accession Number: | edsdoj.82c779b6f58c4a0595d6b3b83034c196 |
Database: | Directory of Open Access Journals |
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RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.jphs.2017.08.006 Languages: – Text: English PhysicalDescription: Pagination: PageCount: 6 StartPage: 8 Subjects: – SubjectFull: Ketamine Type: general – SubjectFull: CYP2C9 Type: general – SubjectFull: Gene polymorphism Type: general – SubjectFull: Metabolism Type: general – SubjectFull: Intrinsic clearance Type: general – SubjectFull: Therapeutics. Pharmacology Type: general – SubjectFull: RM1-950 Type: general Titles: – TitleFull: Function of 38 variants CYP2C9 polymorphism on ketamine metabolism in vitro Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Xiang Zheng – PersonEntity: Name: NameFull: Ping Fang – PersonEntity: Name: NameFull: Su-su Bao – PersonEntity: Name: NameFull: Dan Lin – PersonEntity: Name: NameFull: Jian-ping Cai – PersonEntity: Name: NameFull: Guo-xin Hu IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 09 Type: published Y: 2017 Identifiers: – Type: issn-print Value: 13478613 Numbering: – Type: volume Value: 135 – Type: issue Value: 1 Titles: – TitleFull: Journal of Pharmacological Sciences Type: main |
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