FLUPHENAZINE BLOOD LEVELS, EFFICACY & PHARMACOKINETICS

建议对氟奋乃静（FPZ）的研究进行为期4年的更新 急性口服给药期间的血药浓度、疗效和副作用， 慢性贮库疗法 这项研究获得了两年的资助， 允许开始数据收集，但有关 FPZ放射免疫测定在获得资金之前就已提出要求， 建成 现在有更多的数据支持 分析的有效性，以及早期数据支持 FPZ血浆水平与改善 抗精神病药敏感的病人 建议完成 一个扩大的主要样本的研究，一个额外的样本， 患有精神分裂症和滥用兴奋剂的急性患者，以及 评估血浆高香草酸变化的附加程序 酸（pHVA）和脑解剖异常（MRI）， 反应的预测。 (1)FPZ血浆水平将在四周的治疗期间测量。 急性口服治疗RDC精神分裂症75例， 情感障碍（主要是精神分裂症亚型）。 的 大N将增加统计功效并允许分离 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36例分析 伴有慢性兴奋剂（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)在合作的患者中，pHVA和催乳素对 将研究初始FPZ剂量和治疗4周。 多巴胺（DA）释放和减少的个体差异 精神抑制剂治疗期间DA释放的变化（以pHVA为指标） 可能是治疗作用的重要因素， 抗精神病药，并可能与药物水平相互作用。 无脑 解剖异常（MRI）也可以定义一组 改善、FPZ水平和pHVA之间的相关性更强 提示DA能机制的措施。 (4)将在16名患者中测量FPZ血浆水平， 1年固定剂量FPZ癸酸酯治疗和（在选定的 患者）停药4个月，以评估蓄积， 药物的消失特征及其关系 在口服和长效制剂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.