Function of 38 variants CYP2C9 polymorphism on ketamine metabolism in vitro

Bibliographic Details
Title: Function of 38 variants CYP2C9 polymorphism on ketamine metabolism in vitro
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
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  Data: Function of 38 variants CYP2C9 polymorphism on ketamine metabolism in vitro
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  Data: <searchLink fieldCode="AR" term="%22Xiang+Zheng%22">Xiang Zheng</searchLink><br /><searchLink fieldCode="AR" term="%22Ping+Fang%22">Ping Fang</searchLink><br /><searchLink fieldCode="AR" term="%22Su-su+Bao%22">Su-su Bao</searchLink><br /><searchLink fieldCode="AR" term="%22Dan+Lin%22">Dan Lin</searchLink><br /><searchLink fieldCode="AR" term="%22Jian-ping+Cai%22">Jian-ping Cai</searchLink><br /><searchLink fieldCode="AR" term="%22Guo-xin+Hu%22">Guo-xin Hu</searchLink>
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  Data: Journal of Pharmacological Sciences, Vol 135, Iss 1, Pp 8-13 (2017)
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  Data: Elsevier, 2017.
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  Data: LCC:Therapeutics. Pharmacology
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  Data: <searchLink fieldCode="DE" term="%22Ketamine%22">Ketamine</searchLink><br /><searchLink fieldCode="DE" term="%22CYP2C9%22">CYP2C9</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+polymorphism%22">Gene polymorphism</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolism%22">Metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Intrinsic+clearance%22">Intrinsic clearance</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%2E+Pharmacology%22">Therapeutics. Pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22RM1-950%22">RM1-950</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: 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.
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      – SubjectFull: CYP2C9
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      – SubjectFull: Gene polymorphism
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