Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam

@article{Miura2005IdentificationOH,
  title={Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam},
  author={Masatomo Miura and Koichi Otani and Tadashi Ohkubo},
  journal={Xenobiotica},
  year={2005},
  volume={35},
  pages={455 - 465}
}
To predict drug interactions with estazolam, the biotransformation of estazolam to its major hydoxylated metabolite, 4-hydroxyestazolam was studied in vitro using pooled human liver microsomes and individual expressed human cytochrome P450 (CYP) enzymes. Estazolam was metabolized to 4-hydroxyestazolam according to the Hill kinetic model in pooled human liver microsomes. The Km value for the 4-hydroxylation of estazolam was 24.1 µM, and the Vmax value was 52.6 pmol min−1 mg−1 protein. The… 
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References

SHOWING 1-10 OF 35 REFERENCES
Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes.
TLDR
The results indicated that substrates and inhibitors reported as P450 selective probes are not necessarily specific for individual human P450 forms.
Biotransformation of alprazolam by members of the human cytochrome P4503A subfamily.
TLDR
In adult human liver the CYP3A subfamily members are the principal enzymes involved in the 1'- and 4-hydroxylation of alprazolam, and clinically significant drug drug interactions between alpazolam and other CYP 3A substrates are to be expected.
Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes.
TLDR
Investigation of human liver microsomes for cytochrome P450 isoform-dependent reactions found alpha-Naphthoflavone and furafylline both inhibited phenacetin and 7-ethoxyresorufin O-deethylation processes, a consequence of the absence of CYP1A1 in noninduced human liver.
Midazolam and triazolam biotransformation in mouse and human liver microsomes: relative contribution of CYP3A and CYP2C isoforms.
TLDR
TRZ hydroxylation appears to be CYP3A specific in mice and humans, demonstrating that metabolic profiles of drugs in animals cannot be assumed to reflect human metabolic patterns, even with closely related substrates.
Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors and clinical confirmation of a predicted interaction with ketoconazole.
TLDR
An in vitro-in vivo scaling model predicted a decrement of triazolam clearance due to ketoconazole coadministration that was consistent with the 88% decrement in clearance actually observed in vivo.
Cytochrome P450 inhibitors. Evaluation of specificities in the in vitrometabolism of therapeutic agents by human liver microsomes.
TLDR
Nine chemical inhibitors were selected based on literature data and were examined for their specificity toward cytochrome P450-mediated reactions in human liver microsomes and troleandomycin proved to be the most specific for testosterone 6 beta-hydroxylation.
CYP3A4 is the major CYP isoform mediating the in vitro hydroxylation and demethylation of flunitrazepam.
TLDR
CYP-dependent FNTZ biotransformation, like that of many benzodiazepine derivatives, is mediated mainly by CYP3A, and clinical interactions of FNTz with CYP 3A inhibitors can be anticipated.
Human Drug Metabolism and the Cytochromes P450: Application and Relevance of In Vitro Models
TLDR
This review evaluates the major human hepatic drug‐metabolizing CYP enzymes and their clinically relevant substrates, inhibitors, and inducers and discusses the molecular bases and clinical implications of genetic polymorphisms that affect the CYPs.
Flunitrazepam oxidative metabolism in human liver microsomes: involvement of CYP2C19 and CYP3A4.
TLDR
CYP2C19, CYP3A4 and CYP1A2 mediated the formation of both 3'-hydroxyflunitrazepam and desmethylflunitrazEpam, and investigators need carefully to consider the choice of organic solvent to avoid false CYP identification.
Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms.
TLDR
Since its inhibition is very potent and has a broad "window of selectivity," omeprazole seems to be a useful, selective inhibitor of CYP2C19, and lansoprazole may be the more important in vitro inhibitor of CyP2D6.
...
1
2
3
4
...