FLUPHENAZINE BLOOD LEVELS, EFFICACY AND PHARMACOKINETICS

氟奋乃静的血药浓度、功效和药代动力学

• 批准号: 3380309
• 负责人: GEORGE M SIMPSON
• 金额: $ 14.02万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3380309
• 关键词: drug administration routes; drug metabolism; electrophysiology; fluphenazine; human subject; human therapy evaluation; mental disorder chemotherapy; neuropsychological tests; pharmacokinetics; psychopharmacology; schizophrenia; tranquilizer

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.

本研究拟进行一项为期四年的研究，以探讨（1） 氟奋乃静（FPZ）的血药浓度和治疗急性 精神分裂症急性发作，和（2）口服FPZ的药代动力学， 的FPZ癸酸酯。 治疗期间发现的FPZ浓度较低 （通常低于1 ng/ml）阻碍了血液水平的研究，但更多的 现在已有特异性和灵敏的分析技术。 导频数据 这里提出的建议表明，可能存在最低有效血液水平 大多数患者在口服治疗期间使用FPZ。 建立一个 治疗性血液水平范围对于剂量的调节是有用的 对于个体患者，以及对于神经抑制剂反应性的研究， 生物变量 (1)60例RDC精神分裂症和情感障碍（主要是精神分裂症 亚型）患者将用10，20 或30 mg盐酸氟奋乃静p.o.每日一次，持续28天，随机分组， 双盲条件下，经过一段时间的药物。 血液水平和 基线、第4、7、14、21和28天的临床评级将允许研究 血药浓度、临床变量和不良反应之间的关系。 初始5小时后4小时和24小时的血液水平和临床评估 mg剂量将允许研究稳态水平预测， 早期水平，以及与结果相关的主观反应。 抗精神病药反应，阳性/阴性症状，CAT，神经心理学 和电生理测量，发病前和随访数据将 用本研究和相关研究的数据进行检查。 (2)FPZ癸酸酯治疗期间的血药浓度/疗效关系 值得研究，但这里提供的数据表明，FPZ水平可能 在开始治疗后持续升高较长时间，以及 持续的时间比人们普遍认为的要长。 没有 数据较多，无法选择采样点进行长期临床 问题研究 因此，25名开始FPZ癸酸酯治疗的精神分裂症患者， 将监测随机、固定剂量（12.5或25 mg，每2周一次） 在每次注射前，用血液水平，以获得10个或更多的人， 完成1年的连续注射和4个月的血液水平 停药后。 积累和消失将是 研究了