Effect of High‐Dose Aspirin on CYP2E1 Activity in Healthy Subjects Measured Using Chlorzoxazone as a Probe

@article{Park2006EffectOH,
  title={Effect of High‐Dose Aspirin on CYP2E1 Activity in Healthy Subjects Measured Using Chlorzoxazone as a Probe},
  author={Ji-Young Park and Kyoung-Ah Kim and Pil Whan Park and Jongmyung Ha},
  journal={The Journal of Clinical Pharmacology},
  year={2006},
  volume={46}
}
The authors evaluated the effect of high‐dose aspirin at a therapeutic dose, using chlorzoxazone as a probe for CYP2E1 enzyme activity. In a randomized, open‐label, 2‐way crossover study, 10 healthy men were treated 3 times daily for 6 days with 1 g aspirin or placebo. On day 7, 1 dose of 400 mg chlorzoxazone was administered orally. Plasma concentrations of chlorzoxazone and its metabolite, 6‐hydroxychlorzoxazone, were measured. During the aspirin phase, the area under the time‐concentration… 

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References

SHOWING 1-10 OF 30 REFERENCES

Chlorzoxazone pharmacokinetics as a marker of hepatic cytochrome P4502E1 in humans

Measurement of plasma 6-OH-CZX after administration of a CZX challenge can serve as a marker of hepatic P4502E1 activity and thus help avoid adverse drug reactions secondary to P4501E1 induction, particularly in heavy drinkers.

Effects of aspirin on salivary and serum phenytoin kinetics in healthy subjects

  • J. Paxton
  • Medicine, Biology
    Clinical pharmacology and therapeutics
  • 1980
The results suggest that displacement of DPH from plasma protein binding sites does not result in an increase in free concentration and thus increased pharmacologic activity, but any previous relationship between total serum concentration and therapeutic effect will no longer hold, as a greater proportion of the total concentration will be in the free form and therapeutically active.

Chlorzoxazone, a selective probe for phenotyping CYP2E1 in humans.

It can be asserted that CYP2E1 is the major enzyme involved in chlorzoxazone 6-hydroxylation and that the contribution of CYP3A is very minor.

Toxic interaction between acetazolamide and salicylate: Case reports and a pharmacokinetic explanation

Pharmacokinetic studies in four volunteers showed that the plasma protein binding and renal clearance of acetazolamide were significantly reduced during chronic salicylate dosing, suggesting an interaction with aspirin.

Drug Interactions Involving Aspirin (Acetylsalicylic Acid) and Salicylic Acid

  • J. Miners
  • Medicine, Biology
    Clinical pharmacokinetics
  • 1989
There appear to have been no studies to date which have shown conclusively that aspirin hydrolysis is altered by coadministered drugs, but a number of treatments are known to affect the rate or extent of aspirin absorption, including activated charcoal, antacids, cholestyramine and metoclopramide.

Determination of chlorzoxazone and 6-hydroxychlorzoxazone in human plasma and urine by high-performance liquid chromatography.

  • R. FryeD. Stiff
  • Chemistry, Biology
    Journal of chromatography. B, Biomedical applications
  • 1996

Induction of hepatic cytochrome P4502E1 in rats by acetylsalicylic acid or sodium salicylate.

Human cytochrome P450 2E1 (CYP2E1): from genotype to phenotype.

Despite substantial interindividual variations in chlorzoxazone hydroxylase activity, no relationship between any of the three polymorphisms and CYP2E1 activity was established and, in humans, interindividual variability in CYP 2E1 levels is probably due to differing induction levels as a result of environmental factors, or to genetic factors other than those studied in this work.

Pharmacokinetics of salicylate elimination in man.

  • G. Levy
  • Biology, Chemistry
    Journal of pharmaceutical sciences
  • 1965
The pharmacokinetics of salicylate elimination were found to be unusual both qualitatively and quantitatively, and the results of the present study have potentially important therapeutic, toxicologic, and pharmacogenetic implications.