IMPACT OF LONG-TERM ETHANOL-CONSUMPTION ON CYP1A2 ACTIVITY

Ethanol is a well-known inducer of CYP2E1; whether or not it is an ind ucer of other cytochromes has not been investigated systematically, Th e aim of our study was to evaluate the impact of ethanol consumption o n the activity of CYP1A2, which has been shown to be influenced by dru gs (inhibited or induced). We evaluated CYP1A2 activity by the ratio o f the molar urinary concentrations of the three end products of paraxa nthine demethylation of caffeine to the molar concentration of a parax anthine 8-hydroxylation product, This urinary metabolite ratio has pre viously been shown to correlate with caffeine clearance. The caffeine metabolites were measured in urine collected during the 3 hours after oral administration of 200 mg caffeine. The caffeine test was performe d in 12 smokers (>25 cigarettes/day) and 12 nonsmokers, all of whom we re alcoholic inpatients (daily intake > 100 gm absolute ethanol), with in the first 3 days of their hospital stay and after 14 days of abstin ence from ethanol. In alcoholic patients who were smokers the molar ur inary concentration ratio was 3.14 +/- 0.97 before withdrawal and 4.01 +/- 0.92 after 14 days of abstinence from ethanol. In contrast, in al coholic patients who were nonsmokers it was 2.62 +/- 0.95 and 2.18 +/- 0.96 before and after withdrawal, respectively, In volunteers who wer e smokers the molar urinary concentration ratio was 5.02 +/- 1.51, whe reas in volunteers who were nonsmokers it was 3.22 +/- 1.46. Our resul ts confirm the well-known induction of CYP1A2 activity by tobacco smok ing and show that this induction is masked by long-term ethanol consum ption.