Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls

Fifteen subjects (seven recently abstinent, male, chronic alcoholics and eight, age- and weight-matched male controls) were administered 10 mg 2-hydroxyimipramine (2-OHIMI) by intravenous infusion. Pharmacokinetic parameters were determined from multiple blood samples drawn over 60 hours. Total body clearance of unbound drug, as calculated from the plasma concentration versus time data, was significantly increased in the alcoholic group as compared to the control group (3.12 vs 1.51 L/hr/kg). Terminal elimination half-life was decreased in the alcoholics (7.07 vs 10.12 hr). The fraction of the drug unbound to plasma protein was determined by equilibrium dialysis and was found to be decreased in the alcoholic group over that found in the controls (29.8 vs 36.4%). All subjects were monitored by EKG during the first 4 hours of sampling. Although there was a small mean decrease in heart rate following infusion, it did not achieve statistical significance. Alcoholics had a greater mean increase in P-R but not QTc intervals than control subjects, a difference that was significant at 45 minutes and 1 hour postinfusion. There were no significant differences in the percentage of subjects with abnormal P-R or QTc intervals between the alcoholic and control groups.