Abstract
The objective was to evaluate possible pharmacokinetic and pharmacodynamic interactions for repeated nightly zolpidem dosing with fluoxetine. Twenty-nine healthy female volunteers (mean age, 25.6 years) received 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 plus an evening dose of zolpidem on days 28 through 32. Plasma levels of zolpidem, fluoxetine, and norfluoxetine were determined at the transitions from one regimen to the next. Morning psychomotor tests were performed on days 1, 2, 28, 29, and 33. Steady-state plasma concentrations of fluoxetine/norfluoxetine were reached by day 24 of fluoxetine dosing. 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 concentration, or time to maximal concentration parameters for zolpidem plasma concentrations among nights 1, 28, and 32. There was a statistically significantly increasedt½ for zolpidem on night 32, compared with night 28 (3.64 and 3.29 hr, respectively). There were no significant differences in the next-morning Digit Symbol Substitution Test performance at any time in the study. Both zolpidem and fluoxetine were well tolerated alone or during coadministration. These findings indicate the absence of clinically significant pharmacokinetic or pharmacodynamic interactions between fluoxetine and zolpidem (five consecutive doses) when 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.
Footnotes
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Send reprint requests to: Stéphane Allard, M.D., Lorex Pharmaceuticals, P.O. Box 5110, Chicago, IL 60680-5110.
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Financial support was provided by Lorex Pharmaceuticals, Clinical Research (Skokie, IL).
- Abbreviations used are::
- SSRI
- selective serotonin reuptake inhibitor
- DSST
- Digit Symbol Substitution Test
- C24
- plasma concentration at 24 hr after fluoxetine dosing
- TEAE
- treatment-emergent adverse event
- Cmax
- maximal plasma concentration
- Tmax
- time to maximal plasma concentration
- ANOVA
- analysis of variance
- CYP
- cytochrome P450
- Received November 20, 1997.
- Accepted March 6, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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