EFFECTS OF REBOXETINE & NEFAZODONE ON PHARMACOKINETICS OF ALPRAZOLAM

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Reboxetine, a selective norepinepherine reuptake inhibitor, is an investigational antidepressant which is approved for use in several European countries and for which an NDA will be submitted to the FDA for approval. Once approved, it will join an array of antidepressants which have largely replaced the tricyclic antidepressants. The purpose of this study is to determine whether the pharmacokinetics and pharmacodynamics of alprazolam, a drug whose metabolism is mandated in part by the CYP3A4 isoenzyme, is altered by the administration of reboxetine which is thought to inhibit CYP3A4. The effect of reboxetine on alprazolam will also be compared to that of nefazodone, a seratonin-uptake inhibitor.