MINIMAL INTERACTION BETWEEN FLUOXETINE AND MULTIPLE-DOSE ZOLPIDEM IN HEALTHY WOMEN

The objective was to evaluate possible pharmacokinetic and pharmacodyn amic interactions for repeated nightly zolpidem dosing with fluoxetine . Twenty-nine healthy female volunteers (mean age, 25.6 years) receive d zolpidem (10 mg) and fluoxetine (20 mg) in the following open design : zolpidem on night 1 followed by 1 washout day, a daily morning dose of fluoxetine on days 3 through 27, and a morning dose of fluoxetine p lus an evening dose of zolpidem on days 28 through 32, Plasma levels o f zolpidem, fluoxetine, and norfluoxetine were determined at the trans itions from one regimen to the next. Morning psychomotor tests were pe rformed on days 1, 2, 28, 29, and 33. Steady-state plasma concentratio ns of fluoxetine/norfluoxetine were reached by day 24 of fluoxetine do sing. No significant differences in any pharmacokinetic parameters for fluoxetine and norfluoxetine were observed between day 27 and day 32. There were no significant differences in AUC, maximal plasma concentr ation, or time to maximal concentration parameters for zolpidem plasma concentrations among nights 1, 28, and 32. There was a statistically significantly increased t1/2 for zolpidem on night 32, compared with n ight 28 (3.64 and 3.29 hr, respectively). There were no significant di fferences in the next-morning Digit Symbol Substitution Test performan ce at any time in the study. Both zolpidem and fluoxetine were well to lerated alone or during coadministration. These findings indicate the absence of clinically significant pharmacokinetic or pharmacodynamic i nteractions between fluoxetine and zolpidem (five consecutive doses) w hen the drugs are coadministered to healthy women. Therefore, based on these observations, short-term cotherapy with fluoxetine (20 mg) and zolpidem (10 mg) appears safe.