PHARMACOKINETIC AND PHARMACODYNAMIC EVALUATION OF THE POTENTIAL-DRUG INTERACTION BETWEEN VENLAFAXINE AND DIAZEPAM

To assess possible pharmacokinetic and pharmacodynamic interactions be tween the antidepressant venlafaxine and diazepam, a randomized, two-p eriod, crossover study was conducted in 18 men. Multiple-dose venlafax ine (50 mg every 8 hours) or placebo (double-blind) was given for 10 d ays; on day 4 a single placebo dose (same appearance as diazepam capsu le, single-blind) was given; and on day 5 a single dose of diazepam (1 0 mg) was given. Pharmacokinetic data indicated that diazepam had no s ignificant effect on venlafaxine or O-desmethylvenlafaxine disposition . Diazepam pharmacokinetics were minimally changed in the presence of venlafaxine, Diazepam oral clearance (CL/f) increased slightly (24 +/- 8 versus 26 +/- 6 mL/h/kg; P = .007), volume of distribution (V-z/f) increased (0.85 +/- 0.28 Versus 0.99 +/- 0.34 L/kg; P = .02), and AUC decreased (5973 +/- 2304 versus 5008 +/- 1354 ng . h/mL; P = .02), Ven lafaxine did not alter desmethyldiazepam pharmacokinetics, Pharmacodyn amic data showed a statistically significant diazepam-venlafaxine inte raction for only one of the eight psychometric tests given. Critical f licker fusion slightly decreased (P = .01) between placebo-diazepam (3 7.85 +/- 3.28 Hz) and venlafaxine-diazepam (37.09 +/- 4.13 Hz) treatme nts, The observed pharmacokinetic and pharmacodynamic interactions bet ween diazepam and venlafaxine were small and probably clinically insig nificant.