Atypical Antipsychotics: Determinants of Concentration

非典型抗精神病药：浓度的决定因素

• 批准号: 6655722
• 负责人: BRUCE G POLLOCK
• 金额: $ 26.17万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6655722
• 关键词: Alzheimer's disease; age difference; antipsychotic agents; body composition; clinical trials; clozapine; dosage; fluphenazine; health behavior; human subject; kidney metabolism; patient oriented research; pharmacokinetics; piperazines; psychopharmacology; racial /ethnic difference; risperidone; schizophrenia; serotonin inhibitor; thiazoles

DESCRIPTION (provided by applicant): The primary goal of this revised application (MH64173), which is ancillary to the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), is to reliably capture the concentration exposure of the antipsychotics (risperidone, olanzapine, ziprasidone, fluphenazine, perphenazine, and clozapine) using mixed effect population pharmacokinetic methodologies. The population pharmacokinetic approach is ideally suited for analyzing drug concentration data from large clinical intervention trials because patient-specific as well as overall population pharmacokinetic parameters can be determined using only a few plasma samples per patient. An understanding of pharmacokinetic variability is essential to rational drug prescribing. The population pharmacokinetic approach will permit determination of the extent of variability in drug exposure associated with the use of atypical antipsychotics in large populations under conditions that mirror clinical practice. In addition, the ability of population pharmacokinetic models to capture subjects' drug exposure utilizing single concentration measurements will be assessed in this study. Population pharmacokinetics has also been successfully used to identify sources of variability in drug concentration exposure. Therefore, this ancillary study will provide an innovative way to make optimal use of plasma samples that are being obtained in the CATIE trials. The CATIE trials will recruit up to 2,250 patients providing from 1 to 6 plasma concentration samples per subject for each medication. A separate population pharmacokinetic model will be constructed for each drug incorporating covariate effects. Specific covariates will be then be evaluated as potential contributors to drug exposure variability. Demographic covariates to be examined are age, sex, race/minority status, and body mass index. The potential impact of additional covariates such as prior medication exposure, concomitant medications, smoking status, estimated renal clearance, and treatment adherence will also be assessed. By providing pharmacokinetic data on the atypical antipsychotics under "real world" conditions, this study has broad public health implications, leading to greater awareness of the need to individualize antipsychotics pharmacotherapy for patients suffering from either schizophrenia or Alzheimer's disease.

描述（由申请人提供）：该修订的主要目标 应用（MH64173），它是临床抗精神病药试验的辅助 干预有效性（CATIE）是可靠地捕获浓度 暴露于抗精神病药（利培酮，奥氮平，Ziprasidone， 使用混合作用种群的氟苯胺，泛毒素和氯氮平） 药代动力学方法。人口药代动力学方法是 非常适合分析来自大型临床的药物浓度数据 干预试验是因为患者特异性和总体人口 可以仅使用几个血浆样品确定药代动力学参数 每个患者。对药代动力学变异性的理解对于 理性药物处方。人口药代动力学方法将允许 确定与该药物暴露的变异程度 在大量种群中使用非典型抗精神病药 镜子临床实践。另外，人口的能力 使用单一的药代动力学模型捕获受试者的药物暴露 浓度测量将在本研究中评估。人口 药代动力学也已成功用于识别 药物浓度暴露的变异性。因此，这项辅助研究 将提供一种创新的方法来最佳使用等离子体样本 在CATIE试验中获得。 CATIE审判将招募高达2,250 每个受试者提供1至6个血浆浓度样本的患者 每种药物。单独的种群药代动力学模型将是 为每种融合协变量作用的药物构建。特定的协变量 然后将评估作为药物暴露的潜在贡献者 可变性。被检查的人口协变量是年龄，性别，种族/少数民族 状态和体重指数。此类其他协变量的潜在影响 作为先前的药物暴露，伴随药物，吸烟状况， 还将评估估计的肾脏清除和治疗依从性。经过 提供有关非典型抗精神病药的药代动力学数据 世界“条件”，这项研究具有广泛的公共卫生影响，导致 对抗精神病药的个性化药物疗法的需求更高的认识 对于患有精神分裂症或阿尔茨海默氏病的患者。