File Archive - Ketamine Documents - Contribution of CY3PA4, CYP2B6 and CYP2C9 Isoforms to n-Demethylation of Ketamine in Human Liver Microsomes (2002)

News Groups Blog Forum Chat Video Audio Images Documents Wiki Home

		Drugs Forum > File Archive > Documents > CHEMICAL & (SEMI-) SYNTHETIC DRUGS > Dissociatives Documents > Ketamine Documents
Contribution of CY3PA4, CYP2B6 and CYP2C9 Isoforms to n-Demethylation of Ketamine in Human Liver Microsomes (2002)

Tags

FAQ n Rules

Mark Forums Read

Notices

Create a FREE account now to get access to more forums, more videos, more music, more documents, more images, more reviews, more news about drugs and much more functionality.
Start posting now, join our groups or create your unique profile.

links

Ketamine Documents

Documents about Ketamine, Special K, Ketaject, Ketalar, Ketanest

Allowances: 4.88 Mbytes/1.49 Mbytes used

[RSS Feed]

Entries

Contribution of CY3PA4, CYP2B6 and CYP2C9 Isoforms to n-Demethylation of Ketamine in Human Liver Microsomes (2002)

Left click: open entry/Right click: save entry

Drug Metabolism and Disposition 2002 Jul;30(7):853-8

Hijazi Y, Boulieu R

Ketamine is a widely used drug for its anesthetic and analgesic properties; it is also considered as a drug of abuse, as many cases of ketamine illegal consumption were reported. Ketamine is N-demethylated by liver microsomal cytochrome P450 into norketamine. The identification of the enzymes responsible for ketamine metabolism is of great importance in clinical practice. In the present study, we investigated the metabolism of ketamine in human liver microsomes at clinically relevant concentrations. Liver to plasma concentration ratio of ketamine was taken into consideration. Pooled human liver microsomes and human lymphoblast-expressed P450 isoforms were used. N-demethylation of ketamine was correlated with nifedipine oxidase activity (CYP3A4-specific marker reaction), and it was also correlated with S-mephenytoin N-demethylase activity (CYP2B6-specific marker reaction). Orphenadrine, a specific inhibitor to CYP2B6, and ketoconazole, a specific inhibitor to CYP3A4, inhibited the N-demethylation of ketamine in human liver microsomes. In human lymphoblast-expressed P450, the activities of CYP2B6 were higher than those of CYP3A4 and CYP2C9 at three concentrations of ketamine, 0.005, 0.05, and 0.5 mM. When these results were extrapolated using the average relative content of these P450 isoforms in human liver, CYP3A4 was the major enzyme involved in ketamine N-demethylation. The present study demonstrates that CYP3A4 is the principal enzyme responsible for ketamine N-demethylation in human liver microsomes and that CYP2B6 and CYP2C9 have a minor contribution to ketamine N-demethylation at therapeutic concentrations of the drug

Discussion Thread

Category Ketamine Documents

Submitted by Jatelka

20-06-2007
146.76 Kbytes Hits 45
Keywords: metabolism ketamine cytochrome

Category

Forum Jump

Sitelinks:	Site Functions:
Homepage Wiki Documents Image Gallery Audio Video Forum Blog Groups News	Site Rules Frequently Asked Questions Register to Participate Did you forget your password? All Threads

All times are GMT +1. The time now is 16:28.