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

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

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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.

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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.

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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.

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