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 |
| Access URL: |
https://doaj.org/article/82c779b6f58c4a0595d6b3b83034c196 |
| Accession Number: |
edsdoj.82c779b6f58c4a0595d6b3b83034c196 |
| Database: |
Directory of Open Access Journals |
