Examination of 209 Drugs for Inhibition of Cytochrome P450 2C8

@article{Walsky2005ExaminationO2,
  title={Examination of 209 Drugs for Inhibition of Cytochrome P450 2C8},
  author={Robert L. Walsky and Emily A. Gaman and R. Scott Obach},
  journal={The Journal of Clinical Pharmacology},
  year={2005},
  volume={45}
}
Cytochrome P450 2C8 is involved in the metabolism of drugs such as paclitaxel, repaglinide, rosiglitazone, and cerivastatin, among others. An in vitro assessment of 209 frequently prescribed drugs and related xenobiotics was carried out to examine their potential to inhibit CYP2C8. A validated sensitive, moderate‐throughput high‐performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assay was used to detect N‐desethylamodiaquine, the CYP2C8‐derived major metabolite of… 
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Strong and Selective Inhibitory Effects of the Biflavonoid Selamariscina A against CYP2C8 and CYP2C9 Enzyme Activities in Human Liver Microsomes
TLDR
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References

SHOWING 1-10 OF 43 REFERENCES
The xenobiotic inhibitor profile of cytochrome P4502C8.
AIMS To investigate inhibition of recombinant CYP2C8 by: (i) prototypic CYP isoform selective inhibitors (ii) imidazole/triazole antifungal agents (known inhibitors of CYP), and (iii) certain CYP3A
Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone.
TLDR
CYP2C8 is primarily responsible for the hydroxylation and N-demethylation of rosiglitazone in human liver; with minor contributions from CYP2C9.
Identification of human cytochrome P450s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data
TLDR
The results show that it is possible to make in vitro–in vivo predictions of high, intermediate and low CLint drug categories and the identified CYPs for some of the drugs provide a basis for how these drugs are expected to behave pharmacokinetically and help in predicting drug–drug interactions in vivo.
Drug Interactions of Paclitaxel Metabolism in Human Liver Microsomes
TLDR
The data suggest that special attention should be paid when these drugs are combined in clinical practice, and quercetin, antifungal drugs such as ketoconazole and miconazole, and the antineoplastic drug doxorubicin inhibited formation of 6α-hydroxypaclitaxel.
Regioselective metabolism of taxoids by human CYP3A4 and 2C8: structure-activity relationship.
TLDR
Data strongly suggested that the structure of the lateral chain and the nature of substituent in position 10 play an important role in determining the regioselective oxidation by P450 proteins and modulate the reaction rate by human liver microsomes.
Oxidation of troglitazone to a quinone-type metabolite catalyzed by cytochrome P-450 2C8 and P-450 3A4 in human liver microsomes.
TLDR
The results suggest that in human liver both CYP2C8 and CYP3A4 have major roles in quinone-type metabolite formation and that the hepatic contents of these two P- 450 forms determine which P-450 enzymes play major role in individual humans.
TRIMETHOPRIM AND SULFAMETHOXAZOLE ARE SELECTIVE INHIBITORS OF CYP 2 C 8 AND CYP 2 C 9 , RESPECTIVELY
TLDR
Trimethoprim and sulfamethoxazole can be used as selective inhibitors of CYP2C8 and CYP 2C9 in in vitro studies and in vivo in humans, respectively.
Trimethoprim and sulfamethoxazole are selective inhibitors of CYP2C8 and CYP2C9, respectively.
TLDR
Trimethoprim and sulfamethoxazole can be used as selective inhibitors of CYP2C8 and CYP 2C9 in in vitro studies and in humans, trimethoprises may inhibit the activities of CYC2C7 and CYC9, respectively.
Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid.
TLDR
CYP 2C8*3 is defective in the metabolism of two important CYP2C8 substrates: the anticancer drug paclitaxel and the physiologically important compound arachidonic acid.
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