DECREASE IN CYTOCHROME P4502E1 AS ASSESSED BY THE RATE OF CHLORZOXAZONE HYDROXYLATION IN ALCOHOLICS DURING THE WITHDRAWAL PHASE

To evaluate cytochrome P4502E1 (CYP2E1) induction in alcoholics, the r atio of the concentrations of 6-hydroxychlorzoxazone (6-OH-CHZ) and ch lorzoxazone (CHZ) was measured in blood hr after CHZ ingestion using a HPLC method. This ratio was determined in controls and in alcoholic p atients after 1, 2, 3, 4, 5, 8, and 21 days withdrawal. it was found t o be 0.34 +/- 0.03 in 30 controls and 1.05 +/- 0.14 in 41 alcoholic pa tients within 2 days following ethanol withdrawal. This ratio decrease d rapidly during withdrawal as attested by the short half-life of CYP2 E1, which was found to be 2.5 days, Patients tested for CHZ metabolism after 8 or 21 days alcohol abstinence displayed the same ratio as con trols [0.35 +/- 0.03 (n = 28) and 0.31 +/- 0.03 (n = 34), respectively ]. No correlation was observed between gamma-glutamyltransferase, carb ohydrate-deficient transferrin values, the amount of alcohol consumed/ day, and the 6-OH-CHZ/CHZ ratio. There was no influence of smoking on the rate of CHZ hydroxylation, because smokers displayed the same rati o as nonsmokers [0.33 +/- 0.025 (n = 62) and 0.33 +/- 0.02 (n = 30), r espectively]. The CHZ hydroxylation ratio seems to be a good reflectio n of the hepatic and extrahepatic CYP2E1 activity in humans.