PROLACTIN/FLUPHENAZINE LEVELS IN MAINTENANCE SCHIZOPHREN

维持精神分裂症患者的催乳素/氟奋乃静水平

• 批准号: 3381567
• 负责人: GEORGE M SIMPSON
• 金额: $ 4.18万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3381567
• 关键词: combination chemotherapy; cooperative study; drug adverse effect; drug tolerance; drug withdrawal; family therapy; fluphenazine; human subject; human therapy evaluation; mental disorder chemotherapy; pharmacokinetics; prolactin; psychotropic drugs; relapse /recurrence; schizophrenia; tardive dyskinesia

A four-year study is proposed to investigate (1) the relationship between fluphenazine (FPZ) blood levels and efficacy in the treatment of acute schizophrenic exacerbations, and (2) the pharmacokinetics of oral FPZ and of FPZ decanoate. The small concentrations of FPZ found during treatment (often less than 1 ng/ml) have hindered study of blood levels, but more specific and sensitive assay techniques are now available. Pilot data presented here suggest that there may be a minimum effective blood level of FPZ for most patients during oral treatment. The establishment of a therapeutic blood level range would be useful for the regulation of dosage for individual patients, and for the study of neuroleptic responsiveness as biological variable. (1) Sixty RDC schizophrenic and schizoaffective (mainly schizophrenic subtype) patient with active psychotic symptoms will be treated with 10, 20 or 30 mg of fluphenazine HC1 p.o. daily for 28 days, under randomized, double-blind conditions, after a drug-free period. Bloodlevels and clinical ratings at baseline, 4, 7, 14, 21 and 28 days will permit study of relationships among blood levels, clinical variables and adverse effects. Blood levels and clinical assessments at 4 and 24 hours after the initial 5 mg dose will permit study of the prediction of steady state level from early levels, and of subjective response in relation to outcome. Neuroleptic resonse, positive/negative symptoms, CAT, neuropsychological and electrophysiological measures, premorbid and follow-up data will be examined wiht data from this and associated studies. (2) Blood level/efficacy relationships during treatment with FPZ decanoate deserve investigation, but data presented here suggest that FPZ levels may continue to rise for longer periods after initiation of treatment, and persist for longer periods, than has been generally appreciated. Without more data, sampling points cannot be selected for long-term clinical studies. Therefore, 25 schizophrenic patients starting FPZ decanoate at randomized, fixed doses (12.5 or 25 mg every 2 weeks) will be monitored with blood levels prior to each injection, to obtain 10 or more who have completed 1 year of consecutive injections and 4 months of blood levels after discontinuation of drug. Accumulation and disappearance will be studied.

建议进行一项为期四年的研究，以调查(1) 氟奋乃静治疗急性心肌梗死的血药浓度及疗效 精神分裂症的恶化，以及(2)口服福美沙星和 加氟辛酸甲酯。在治疗过程中发现的小浓度的FPZ (通常低于1 ng/ml)阻碍了对血液水平的研究，但更多的是 现在已经有了特异和灵敏的检测技术。试点数据 这表明可能存在一个最低有效血液水平 大多数患者在口腔治疗过程中会使用氟苯吡啶。成立了一个 治疗性血液水平范围将有助于剂量的调节。 对于个别患者，以及对精神安定剂反应性的研究 生物变量。 (1)60例RDC精神分裂症和分裂情感性(主要为精神分裂症) 亚型)有活跃精神症状的患者将接受10，20 或30毫克盐酸氟奋乃静口服。每天28天，在随机的情况下， 在戒毒期过后，出现双盲情况。血液水平和 基线、4天、7天、14天、21天和28天的临床评分将允许研究 血药浓度、临床变量和不良反应之间的关系。 首次5次服药后4小时和24小时的血药浓度和临床评估 镁剂量将允许研究从 早期水平，以及主观反应与结果的关系。 抗精神病药物共振，阳性/阴性症状，CAT，神经心理学 和电生理测量，病前和随访数据将 检查了来自这项研究和相关研究的数据。 (2)治疗过程中的血药浓度/疗效关系 值得研究，但这里提供的数据表明，FPZ水平可能 在开始治疗后持续较长时间的上升，以及 持续的时间比人们普遍认识到的要长。如果没有 数据较多，长期临床不能选择采样点 学习。因此，25名精神分裂症患者开始服用FPZ时， 将监测随机、固定剂量(每两周12.5或25毫克) 与每次注射前的血液水平，以获得10名或更多的人 完成1年的连续注射和4个月的血药水平 在停药后。积累和消失将是 学习。