Studies on induction of metabolism of ethyl carbamate in mice by ethanol

Acute administration of ethanol, acetaldehyde, dimethyl sulfoxide and several other compounds has been reported previously by this laboratory to inhibit the metabolism of ethyl carbamate (E.C.) in mice. Since many enzyme systems that are inhibited by a compound are also induced by that chemical, the effect of chronic administration of ethanol on the metabolism of E.C. was studied in male, A/JAX mice. Ethanol was given in three pretreatment schedules: 1, 5% in drinking water for 7 days with a 24-hr washout before E.C.; 2, 10% in drinking water 48-12 hr before E.C.; 3, 5 g/kg orally as 10% in saline 48 and 24 hr before E.C. E.C. (11.125 mg/kg) in saline was administered orally and blood samples taken at frequent intervals for analysis of E.C. by a GC/MS technique developed in this laboratory. AUCs of E.C. concentration vs. time were calculated by trapezoidal estimation. From these data, E.C. blood clearance values (dose/AUC; ml hr-1kg-1) were calculated: control, 751 +/- 49.7; group 1,803 +/- 43.5; group 2, 1225 +/- 24.6; group 3, 815 +/- 75.4. Only group 2 was significantly different (p less than 0.01) from control and other groups by Newman-Keuls test. These results indicate that ethanol may be an inducer of E.C. metabolism only under certain limited conditions. The induction may be detected 12 hr after ethanol administration but is not apparent at 24 hr after ethanol pretreatment.