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… Expand
Evaluation of 227 Drugs for In Vitro Inhibition of Cytochrome P450 2B6
TLDR
Inhibitors of CYP2B6 were identified from a wide variety of therapeutic classes and clopidogrel and ticlopidine were identified as being of concern as potential inhibitors of clinical relevance. Expand
SELECTIVE INHIBITION OF HUMAN CYTOCHROME P4502C8 BY MONTELUKAST
TLDR
In vitro data support the use of montelukast as a selective CYP2C8 inhibitor that could be used to determine the contribution of this enzyme to drug metabolism reactions, and raise the possibility that montelUKast could have an effect on the metabolic clearance of drugs possessing CYP 2C8-catalyzed metabolism as a major clearance pathway, thereby eliciting pharmacokinetic drug-drug interactions. Expand
Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions
TLDR
Current knowledge on substrates, inhibitors, inducers, and pharmacogenetics of CYP2C8, as well as its role in clinically relevant drug interactions is reviewed. Expand
Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity
The majority of marketed small-molecule drugs undergo metabolism by hepatic Cytochrome P450 (CYP) enzymes (Rendic 2002). Since these enzymes metabolize a structurally diverse number of drugs,Expand
Cytochrome P450 enzymes— in vitro , in vivo , and in silico studies
Metabolism is a major determinant of the pharmacokinetic properties of most drugs and is often behind bioavailability problems, drug-drug interactions, and metabolic idiosyncrasies. Cytochrome P450Expand
Direct inhibition of Re Du Ning Injection and its active compounds on human liver cytochrome P450 enzymes by a cocktail method.
TLDR
Investigating the direct inhibitory effects of Re Du Ning Injection and its active compounds on the major cytochrome P450 enzyme (CYP) isoforms of human liver microsomes suggested that drug-drug interactions may occur and great caution should be taken when RDN is combined with drugs metabolized by these CYPs. Expand
Further Assessment of 17α-Ethinyl Estradiol as an Inhibitor of Different Human Cytochrome P450 Forms in Vitro
TLDR
The results implicate intestinal CYP1A1, and possibly CYP2C19, as the loci of EE drug interactions with highly extracted drugs like MEL, which raises the possibility that the concentration of EE during first pass may exceed 1000 nM, sufficient to affect CYP3A4 and other P450s. Expand
Pharmacokinetic Drug Interactions Involving 17α-Ethinylestradiol
TLDR
This article summarises what is known of the drug-metabolising enzymes and transporters governing the metabolism, disposition and excretion ofα-Ethinylestradiol and related information to known clinical drug-drug interactions. Expand
Effect of pterostilbene on in vitro drug metabolizing enzyme activity
  • A. Albassam, R. Frye
  • Medicine, Chemistry
  • Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society
  • 2019
TLDR
It is indicated that pterostilbene inhibits CYP2C8 and UTG1A6 activity in vitro and may inhibit metabolism by these enzymes in vivo, and clinical studies are warranted to evaluate the in vivo relevance of these interactions. Expand
The Development of a Cocktail CYP2B6, CYP2C8, and CYP3A5 Inhibition Assay and a Preliminary Assessment of Utility in a Drug Discovery Setting
TLDR
In this study, a single cocktail inhibition assay for the three enzymes is developed and its utility in drug discovery is assessed and the potential impact of these findings on a cytochrome P450 inhibition strategy is discussed. Expand
...
1
2
3
4
5
...

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 CYP3AExpand
Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans.
TLDR
Five in vitro approaches have been used to identify the P450 isoforms responsible for the human liver microsomal oxidation of montelukast, and experimental results consistently indicated that CYP3A4 catalyzes sulfoxidation and 21-hydroxylation, whereas CYP2C9 selectively mediates methyl-hydoxylation. Expand
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. Expand
Potent inhibition of yeast-expressed CYP2D6 by dihydroquinidine, quinidine, and its metabolites.
TLDR
Quinidine and the impurity dihydroquinidine are the important inhibitors of CYP2D6, as determined by the retention-time parameter k' using reverse-phase HPLC. Expand
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. Expand
Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver microsomes: comparison of Ki values and impact of CYP3A5 expression.
TLDR
It is concluded that there is no significant difference in inhibition type and affinity of ketoconazole and fluconazole for hepatic versus intestinal CYP3A4, and there can be significant differences in the affinity of these two enzymes for inhibitors. Expand
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. Expand
Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate.
TLDR
Data show that CYP2C8 is the main hepatic isoform responsible for the metabolism of AQ, and the specificity, high affinity, and high turnover make AQ desethylation an excellent marker reaction for CYP1C8 activity. Expand
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. Expand
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. Expand
...
1
2
3
4
5
...