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）：本次修订的主要目标 申请（MH64173），是临床抗精神病药试验的辅助 干预有效性（CATIE）的目的是可靠地捕获浓度 接触抗精神病药物（利培酮、奥氮平、齐拉西酮、 使用混合效应群体（氟奋乃静、奋乃静和氯氮平） 药代动力学方法。群体药代动力学方法是 非常适合分析来自大型临床的药物浓度数据 干预试验因为患者特定以及总体人群 仅使用少量血浆样品即可确定药代动力学参数 每个病人。了解药代动力学变异性对于 合理用药。群体药代动力学方法将允许 确定与药物暴露相关的变异程度 在大量人群中使用非典型抗精神病药物 反映临床实践。另外，人口的能力 药代动力学模型利用单一数据来捕获受试者的药物暴露 本研究将评估浓度测量。人口 药代动力学也已成功用于鉴定来源 药物浓度暴露的变异性。因此，本次辅助研究 将提供一种创新的方法来充分利用血浆样本 在 CATIE 试验中获得。 CATIE 试验将招募多达 2,250 名 患者为每个受试者提供 1 至 6 个血浆浓度样本 每种药物。一个单独的群体药代动力学模型将是 为每种包含协变量效应的药物构建。具体协变量 然后将被评估为药物暴露的潜在因素 可变性。要检查的人口统计协变量是年龄、性别、种族/少数民族 状态和体重指数。额外协变量的潜在影响，例如 如先前的药物暴露、伴随药物、吸烟状况、 估计的肾脏清除率和治疗依从性也将被评估。经过 在“真实”下提供非典型抗精神病药物的药代动力学数据 世界”条件下，这项研究具有广泛的公共卫生影响，导致 更加认识到个体化抗精神病药物治疗的必要性 对于患有精神分裂症或阿尔茨海默病的患者。