Dose-response evaluation of the interaction between sertraline and alprazolam in vivo

In vitro data show the inhibition of alprazolam metabolism by sertraline vi a CYP3A4; therefore, using a randomized, double-blind placebo-controlled de sign, the authors conducted this study to assess the potential for similar in vivo inhibition in humans. Ten healthy volunteers participated in two te st sessions (placebo/alprazolam 1 mg orally) before the initiation of sertr aline treatment. Blood samples were obtained over a 32-hour period and phar macodynamic measures (sedation, psychomotor performance, memory function) w ere obtained over an 8-hour period. After a minimum of 2 weeks of daily ser traline self-administration (50, 100, or 150 mg/day), test sessions were re peated. Alprazolam concentrations (N = 6, 4, and 6 at sertraline doses of 5 0, 100, and 150 mg/day, respectively) showed no significant changes based o n peak concentration (C-max), time to maximum concentration (T-max), elimin ation half-life (t(1/2[beta])), and area under the concentration-time curve (AUC(0-infinity)) with the exception of a reduced C-max in the 50 mg/day g roup. Similarly, dynamic data showed no significant variations based on pea k effect, T-max, and AUC(0-8), with the exception of increased peak impairm ent in one measure of psychomotor performance. No differences were detected between placebo alone and placebo pins sertraline. These findings suggest that sertraline (50-150 mg/day) does not alter the single-dose kinetics or dynamics of alprazolam; therefore, the combination may be prescribed withou t an increased risk of alprazolam toxicity.