Bigos Kristin L, Bies Robert R, Pollock Bruce G
Department of Pharmaceutical Sciences, University of Pittsburgh, School of Pharmacy, Pittsburgh, PA 15261, USA.
Am J Geriatr Psychiatry. 2006 Dec;14(12):993-1003. doi: 10.1097/01.JGP.0000224330.73063.6c.
Although geriatric patients are the major recipients of drugs, most research during drug development is conducted in healthy younger adults. Safe and effective drug therapy in the elderly requires an understanding of both drug disposition and response in older individuals. One of the major issues in studying the elderly relates to the ability to study a large number of people in a minimally invasive way. Population pharmacokinetics can be used to model drug concentrations from a large population of sparsely sampled individuals. Population pharmacokinetics characterizes both the interindividual (between-subject) and intraindividual (within-subject) variability, and can identify factors that contribute to pharmacokinetic and pharmacodynamic variability. Population pharmacokinetics can be used to aid in designing large clinical trials by simulating virtual data based on the study design. It can also be used to assess consistency of drug exposure and evaluate its effect on clinical outcome. This article reviews the methods used in pharmacokinetic modeling, as well as providing examples of population pharmacokinetic modeling, highlighting its application to geriatric psychiatry.
尽管老年患者是药物的主要使用者,但药物研发过程中的大多数研究是在健康的年轻人中进行的。对老年人进行安全有效的药物治疗需要了解老年人的药物处置情况和反应。研究老年人的主要问题之一涉及以微创方式研究大量人群的能力。群体药代动力学可用于对大量稀疏采样个体的药物浓度进行建模。群体药代动力学表征个体间(受试者间)和个体内(受试者内)的变异性,并可识别导致药代动力学和药效学变异性的因素。群体药代动力学可用于通过基于研究设计模拟虚拟数据来辅助设计大型临床试验。它还可用于评估药物暴露的一致性并评估其对临床结果的影响。本文回顾了药代动力学建模中使用的方法,并提供了群体药代动力学建模的示例,重点介绍了其在老年精神病学中的应用。