DeVane C Lindsay
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Psychopharmacol Bull. 2003 Spring;37 Suppl 1:29-41.
The development of paroxetine hydrochloride began in the late 1970s. An abundance of data have been accumulated from clinical investigations demonstrating the efficacy of paroxetine in the treatment of major depression and anxiety disorders. The published literature contains a substantial amount of supportive data documenting the safety, tolerability, and pharmacokinetic and pharmacodynamic properties of paroxetine. The role of paroxetine in clinically significant drug-drug interactions, especially involving metabolic inhibitory effects on the substrates of cytochrome p450 2D6, has long been suspected, but only isolated cases provide any evidence. Published data for widespread patient morbidity from drug interactions with paroxetine are almost nonexistent. Considerations of the pharmacokinetic properties of paroxetine support a rationale for the development of new dosage forms that maintain the efficacy yet improve the tolerability profile of the selective serotonin reuptake inhibitors. Paroxetine controlled-release is an enteric-coated formulation with release features that may enhance clinical outcome by modifying absorption-related pharmacokinetics, improving tolerability, and maintaining therapeutic benefits
盐酸帕罗西汀的研发始于20世纪70年代末。临床研究积累了大量数据，证明帕罗西汀在治疗重度抑郁症和焦虑症方面的疗效。已发表的文献包含大量支持性数据，记录了帕罗西汀的安全性、耐受性以及药代动力学和药效学特性。长期以来，人们一直怀疑帕罗西汀在具有临床意义的药物相互作用中的作用，尤其是对细胞色素P450 2D6底物的代谢抑制作用，但只有个别案例提供了相关证据。几乎没有关于帕罗西汀药物相互作用导致广泛患者发病的已发表数据。对帕罗西汀药代动力学特性的考虑为开发新剂型提供了理论依据，这些新剂型既能保持疗效，又能改善选择性5-羟色胺再摄取抑制剂的耐受性。帕罗西汀控释制剂是一种肠溶包衣制剂，其释放特性可通过改变与吸收相关的药代动力学、提高耐受性和维持治疗效果来增强临床疗效。
