EFFECTS OF REBOXETINE & NEFAZODONE ON PHARMACOKINETICS OF ALPRAZOLAM

瑞波西汀是一种选择性去甲肾上腺素再摄取抑制剂，是一种研究用抗抑郁药，已在几个欧洲国家获得批准，其NDA将提交FDA批准。一旦获得批准，它将加入一系列抗抑郁药的行列，这些药物在很大程度上已经取代了三环类抗抑郁药。这项研究的目的是确定阿普唑仑的药代动力学和药效学是否因给予瑞波西汀而改变，瑞波西汀被认为抑制CYP3A4。阿普唑仑的代谢部分由CYP3A4同工酶控制。瑞波西汀对阿普唑仑的疗效也将与5-羟色胺摄取抑制剂奈法唑酮进行比较。

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.