Assessment of cytochrome P4502E1 induction in alcoholic patients by chlorzoxazone pharmacokinetics

Biochem Pharmacol. 1994 Apr 29;47(9):1503-8. doi: 10.1016/0006-2952(94)90524-x.


Chlorzoxazone is mainly metabolized to 6-hydroxychloroxazone (6-OHchlorzoxazone) by the ethanol-inducible cytochrome P450 2E1 (CYP2E1). To evaluate the impact of ethanol consumption on the enzyme induction, the pharmacokinetics of chlorozoxazone and 6-OHchlorzoxazone were studied in alcoholic and control subjects. Fifteen alcoholic male inpatients (all smokers, daily intake 333 +/- 191 g of absolute ethanol) and 20 healthy male volunteers (10 smokers and 10 non-smokers, weekly intake < 100 g of absolute ethanol) participated in this study. Following a 12 hr fasting period, each subject was orally administered 500 mg of chlorzoxazone. Venous blood and urine samples were collected over a 10 hr period. Areas under the curve of plasma concentration versus time (AUC) of chlorzoxazone and 6-OHchlorzoxazone was calculated. The total plasma clearance of chlorzoxazone was measured as the dose/AUC ratio. The mean total plasma clearance was not different between smoker and non-smoker controls but it was enhanced by 73% in alcoholic patients. These results indicate a negligible and non-significant effect of cigarette smoking in controls but an increased metabolism of chlorzoxazone in alcoholic patients (P < 0.05). This increase was corroborated by the 2-fold enhancement of the 6-OHchlorzoxazone/chlorzoxazone AUC ratio, compared to controls. A good correlation was found between this AUC ratio and the 6-OHchlorzoxazone/chlorzoxazone concentration ratio at t = 2 hr in patients and in controls (r = 0.88 and 0.85, respectively, P < 0.01). The concentration ratio increased by 150% in alcoholic patients and decreased by 65% in the seven alcoholics tested after 7 days of alcohol abstinence. It is therefore concluded that the 6-OHchlorzoxazone/chlorzoxazone concentration ratio at t = 2 hr could constitute a simple and non-traumatic marker of CYP2E1 induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Alcoholism / blood
  • Alcoholism / enzymology*
  • Aspartate Aminotransferases / blood
  • Chlorzoxazone / analogs & derivatives
  • Chlorzoxazone / pharmacokinetics*
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Enzyme Induction / drug effects
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • gamma-Glutamyltransferase / blood


  • 6-hydroxychlorzoxazone
  • Cytochrome P-450 Enzyme System
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Chlorzoxazone