FLUPHENAZINE BLOOD LEVELS, EFFICACY & PHARMACOKINETICS

一项氟奋乃静(FPZ)的研究被提议续期四年 急性经口服药期间的血药浓度、疗效和副作用 慢性仓库疗法。这项研究得到了两年的资助，以 允许启动数据收集，但关于以下方面的进一步数据 在资助之前要求进行FPZ放射免疫分析 完成了。现在有更多的数据支持 化验的有效性，以及支持 FPZ血浆水平与心绞痛改善的关系 对抗精神病药有反应的病人。建议完成以下工作： 用扩大的主要样本进行研究，额外的样本 精神分裂症和兴奋剂滥用的急性患者，以及 评估血浆高香草酸变化的其他程序 酸(PHVA)和脑解剖异常(MRI)AS 反应的预测者。 (1)将在4周内测量FPZ血浆水平 急性口服治疗RDC精神分裂症75例 分裂情感性(主要是精神分裂症亚型)障碍。这个 大N将增加统计能力，并允许分开 对符合改善标准的患者进行分析。 (2)慢性综合征型精神分裂症患者36例 并发慢性兴奋剂(单独或多种物质)滥用 将在一个相同的设计中进行尖锐的研究。 (3)在合作患者中，PHVA和催乳素对An的反应 将研究初始的FPZ剂量和至4周的治疗。 多巴胺(DA)释放和减少的个体差异 抗精神病药物治疗期间DA释放的变化(以PHVA为指标) 可能是其治疗作用中的重要因素 神经阻滞剂，并可能与药物水平相互作用。脑缺乏症 解剖异常(MRI)也可定义为 改善程度、FPZ水平和PHVA之间存在较强的相关性 提示DA-ERIC机制的措施。 (4)将在16名患者中测量FPZ的血浆水平 1年固定剂量的FPZ癸酸盐治疗和(在选定的 患者)停药4个月，以评估药物的累积和 毒品的消亡特征及其与毒品的关系 在口腔和仓库治疗期间的水平之间。

A four-year renewal is proposed of a study of fluphenazine (FPZ) blood levels, efficacy and side effects during acute oral and chronic depot therapy. This study was funded for two years to permit initiation of data collection, but further data concerning the FPZ radioimmunoassay were requested prior to funding to completion. Further data are now available supporting the validity of the assay, as well as early data supporting a relationship between FPZ plasma levels and improvement in neuroleptic-responsive patients. It is proposed to complete the study with an enlarged primary sample, an additional sample of acute patients with schizophrenia and stimulant abuse, and additional procedures to assess changes in plasma homovanillic acid (pHVA) and brain anatomic abnormalities (by MRI) as predictors of response. (1) FPZ plasma levels will be measured during four weeks of acute oral treatment of 75 patients with RDC schizophrenic and schizoaffective (mainly schizophrenic subtype) disorders. The large N will increase statistical power and permit separate analysis of patients meeting a criterion of improvement. (2) A sample of 36 patients with chronic syndromal schizophrenia complicated by chronic stimulant (alone or polysubstance) abuse will be studied acutely in an identical design. (3) In cooperating patients, pHVA and prolactin response to an initial FPZ dose and to 4 weeks of treatment will be studied. Individual differences in dopamine (DA) release and in reduction of DA release during neuroleptic treatment (as indexed by pHVA) may be important factors in the therapeutic action of neuroleptics, and may interact with drug levels. Absence of brain anatomic abnormalities (MRI) may also define a group with stronger correlations among improvement, FPZ level and pHVA measures suggesting DA-ergic mechanisms. (4) FPZ plasma levels will be measured in 16 patients during up to 1 year of fixed dose FPZ decanoate therapy and (in selected patients) 4 months of drug withdrawal, to assess accumulation and disappearance characteristics of the drug and the relationship between levels during oral and depot treatment.