Inhibition of chlorzoxazone metabolism, a clinical probe for CYP2E1, by a single ingestion of watercress

  title={Inhibition of chlorzoxazone metabolism, a clinical probe for CYP2E1, by a single ingestion of watercress},
  author={Isabelle A. Leclercq and Jean Pierre Desager and Yves Horsmans},
  journal={Clinical Pharmacology \& Therapeutics},
Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans.
For prevention of CYP2E1-mediated bioactivation, depending on protoxicant disposition, a second DSF dose might be necessary to completely prevent toxicity, and results regarding CYP 2E1 disposition may be useful for modeling the effects of CYE1 inducers and inhibitors.
Consumption of watercress fails to alter coumarin metabolism in humans.
Under the conditions of the study, PEITC and other constituents of watercress had at most a marginal inhibitory effect on P450 2A6-catalyzed coumarin 7-hydroxylation.
Inhibition of Cytochrome P450 (CYP450) Isoforms by Isoniazid: Potent Inhibition of CYP2C19 and CYP3A
Inhibition of one or both CYP2C19 and CYP3A isoforms is the likely mechanism by which INH slows the elimination of coadministered drugs, including phenytoin, carbamazepine, diazepam, triazolam, and primidone.
Watercress has no Importance for the elimination of ethanol by CYP2E1 inhibition.
In healthy volunteers, no major watercress effect was observed on ethanol clearance but a weak inhibiting effect on acetaldehyde metabolism is possible, and ethanol absorption is also delayed by single ingestion of watercressing immediately preceding ethanol consumption.
Genetic and dietary predictors of CYP2E1 activity: a phenotyping study in Hawaii Japanese using chlorzoxazone.
  • L. Marchand, G. Wilkinson, L. Wilkens
  • Medicine
    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
  • 1999
It was indicated that body weight was a major contributor to the interindividual variability in the oral clearance of chlorzoxazone, accounting for 43% of the variance, and consumption of lettuce, broccoli, and black tea explained additional components of the variability, as did medication use, age, and CYP2E1 genotype.
The Inactivation of Human CYP2E1 by Phenethyl Isothiocyanate, a Naturally Occurring Chemopreventive Agent, and Its Oxidative Bioactivation
The data suggest that the metabolism of PEITC by CYP2E1 that results in the inactivation of CYP1E1 may occur by a mechanism similar to that observed with other sulfur-containing compounds, such as parathion.
Effect of Simultaneous Induction and Inhibition of CYP3A by St John's Wort and Ritonavir on CYP3A Activity
Induction may be unmasked after the withdrawal of a combination of a potent CYP3A inhibitor and a potent cytochrome P450 3A (CYP3A) inducer, leading to substantial drops in drug exposure of CYP 3A substrates.
Human variability for metabolic pathways with limited data (CYP2A6, CYP2C9, CYP2E1, ADH, esterases, glycine and sulphate conjugation).
  • J. Dorne, K. Walton, A. Renwick
  • Medicine, Biology
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2004
Response: Similar effect of quercetin on CYP2E1 and CYP2C9 activities in humans?
This study suggests that treatment with quercetin 500 mg twice daily for 10 days significantly enhanced the exposure of chlorzoxazone, a CYP2E1 substrate, in healthy subjects, and the metabolic ratios of diclofenac and chlorzxazone were significantly affected by quercETin when compared with previous herb-drug interaction studies.
Cytochrome P450 Inactivation by Pharmaceuticals and Phytochemicals: Therapeutic Relevance
This review summarizes the catalytic efficiencies of many inactivator drugs along with any consequent clinical relevance and ranked the chemical agents described for the kinetic efficiency of inactivation and contrasted with the known clinically relevant drug interactions.


Single‐dose disulfiram inhibition of chlorzoxazone metabolism: A clinical probe for P450 2E1
It is shown that a single dose of disulfiram significantly diminishes the activity of human P450 2E1 in vivo, which suggests that this modality for manipulating clinical P4502E1 activity may provide a useful probe for delineating P450 3E1 participation in human drug biotransformation or for the treatment of poisoning by P450 1E1‐activated toxins.
Modulation of CYP2E1 activity by isoniazid in rapid and slow N-acetylators.
The interphenotypic difference in the time-dependent interactions of isoniazid with CYP2E1 probably reflect a higher drug exposure in slow acetylators.
Chlorzoxazone is metabolized by human CYP1A2 as well as by human CYP2E1.
Questions are raised about the suitability of chlorzoxazone as an in vivo probe for hepatic CYP2E1 activity after the specificity of such a substrate was studied using vaccinia virus expressed human P450 forms and the effect of inhibitors for chlorz oxazone metabolism by human liver microsomes was studied.
Inhibition and induction of cytochrome P4502E1‐catalyzed oxidation by isoniazid in humans
The time course of the interaction with regard to chlorzoxazone elimination and formation is compatible with an inhibition‐induction effect of isoniazid on cytochrome P4502E1, and the mechanism of this biphasic effect is probably induction by protein stabilization, which results in inhibition of catalytic activity while isoniaZid is present.
Contribution of human CYP3A subfamily members to the 6-hydroxylation of chlorzoxazone.
CYP3A may make a significant contribution to CHZ 6-hydroxylation and therefore caution should be exercized when chlorzoxazone is employed as a specific 2E1 probe in vitro and in vivo.
In vivo and in vitro characterization of CYP2E1 activity in Japanese and Caucasians.
Data show an interracial difference in CYP2E1 activity, which may account, in part, for the lower rate of some cancers, e.g., lung cancer, in Japanese compared to Caucasians men.
Biotransformation of Chlorzoxazone by Heptatic Microsomes from Humans and Ten Other Mammalian Species
DDC, a CYP2E1 inhibitor in humans, was a potent mechanism‐based inhibitor of 6OH‐CLZ formation in microsomes from all species examined and significantly enhanced the maximum degree of inhibition but had no effect on inhibitor potency.