Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes.

@article{Hijazi2002ContributionOC,
  title={Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes.},
  author={Youssef Hijazi and Roselyne Boulieu},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2002},
  volume={30 7},
  pages={
          853-8
        }
}
  • Y. Hijazi, R. Boulieu
  • Published 1 July 2002
  • Chemistry, Medicine
  • Drug metabolism and disposition: the biological fate of chemicals
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… 
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Inhibition of cytochrome P450 enzymes involved in ketamine metabolism by use of liver microsomes and specific cytochrome P450 enzymes from horses, dogs, and humans.
TLDR
Ketamine N-demethylation was stereoselective in single human CYP3A4 and canine CYP2C21 enzymes and to address drug-drug interactions in these animal species, investigations with single CYPs are needed.
The CYP2B6*6 Allele Significantly Alters the N-Demethylation of Ketamine Enantiomers In Vitro
TLDR
Results indicate a major role of CYP2B6 in ketamine N-demethylation in vitro and a significant impact of the CYP 2B6*6 allele on enzyme-ketamine binding and catalytic activity.
Enantioselective capillary electrophoresis for identification and characterization of human cytochrome P450 enzymes which metabolize ketamine and norketamine in vitro.
TLDR
This is the first study elucidating the individual enzymes responsible for hydroxylation of norketamine and suggesting that in vitro biotransformation of ketamine and norkettamine is stereoselective.
In vitro evaluation of differences in phase 1 metabolism of ketamine and other analgesics among humans, horses, and dogs.
TLDR
Higher concentrations and diminished clearance of ketamine may cause adverse effects when administered concurrently with other analgesics, and Enzymes of the CYP 3A4 family and orthologs of CYP 2C9 were involved in ketamine metabolism in horses, dogs, and humans.
Role of Cytochrome P4502B6 Polymorphisms in Ketamine Metabolism and Clearance
TLDR
These results show that while the CYP2B6*6 polymorphism results in diminished ketamines metabolism in vitro, this allelic variant did not affect single, low-dose ketamine metabolism, clearance, and pharmacokinetics in vivo.
Potent inhibition of cytochrome P450 2B6 by sibutramine in human liver microsomes.
TLDR
In vitro data support the use of sibutramine as a well-known inhibitor of CYP2B6 for routine screening of P450 reversible inhibition when human liver microsomes are used as the enzyme source.
Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes
TLDR
The formation rate of DLOP showed biphasic kinetics, suggesting the involvement of multiple P450 isoforms, and among them, CYP2C8 and CYP3A4 may play a crucial role in LOP metabolism at the therapeutic concentrations of LOP.
Role of the equine CYP3A94, CYP3A95 and CYP3A97 in ketamine metabolism in presence of medetomidine, diazepam and methadone studied by enantioselective capillary electrophoresis.
TLDR
Differences in ketamine N-demethylation in combination with diazepam and methadone are unlikely to be of clinical relevance because ketamine and the other drugs do not have a small therapeutic margin.
Equine cytochrome P450 2B6--genomic identification, expression and functional characterization with ketamine.
TLDR
Equine CYP2B6 was determined to be a CYP enzyme involved in ketamine and norketamine metabolism, thus confirming results from inhibition studies with horse liver microsomes.
Effects of medetomidine and its active enantiomer dexmedetomidine on N‐demethylation of ketamine in canines determined in vitro using enantioselective capillary electrophoresis
TLDR
S‐ketamine combined with dexmedetomidine should be the best option for canines and the enantioselective CE assay with highly sulfated γ‐cyclodextrin as chiral selector is an effective tool for determining kinetic and inhibition parameters of metabolic pathways.
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