A PHARMACOKINETIC AND PHARMACODYNAMIC EVALUATION OF THE COMBINED ADMINISTRATION OF ALPRAZOLAM AND FLUVOXAMINE

We have assesed the pharmacokinetic and pharmacodynamic interaction be tween fluvoxamine, a seratonin reuptake inhibitor, and alprazolam, a t riazolobenzodiazepine. Healthy men took fluvoxamine maleate daily for 10 days (50 mg on days 1-3, 100 mg on days 4-10) (n = 20), 1 mg of alp razolam four times daily for four days (days 7-10 of the study period) (n = 20), or a combination of the two (n = 20), according to a parall el study design. Alprazolam and fluvoxamine concentrations were measur ed in serial plasma samples by HPLC and gas chromatography respectivel y, and psychomotor performance and memory were assessed on days 1, 7, and 10. Fluvoxamine increased plasma alprazolam concentrations by 100% . The mean apparent half-life of alprazolam was increased from 20 h to 34 h after fluvoxamine co-administration. The increased plasma concen trations of alprazolam resulted in significantly greater reductions in psychomotor performance evident on day 10. Mean fluvoxamine plasma co ncentrations were about 25% lower in those who took the combination th an in those who took only fluvoxamine; this was more likely due to het erogeneity between the treatment groups than to an effect of alprazola m. The dosage of alprazolam should be reduced during co-administration with fluvoxamine.