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老年患者中拉莫三嗪的群体药代动力学

Population pharmacokinetics of lamotrigine in elderly patients.

作者信息

Punyawudho Baralee, Ramsay R Eugene, Macias Flavia M, Rowan A James, Collins Joseph F, Brundage Richard C, Birnbaum Angela K

机构信息

Experimental and Clinical Pharmacology, University of Minnesota, 7-170 WDH, 308 Harvard St SE, Minneapolis, MN 55455, USA.

出版信息

J Clin Pharmacol. 2008 Apr;48(4):455-63. doi: 10.1177/0091270007313391. Epub 2008 Feb 22.

Abstract

Lamotrigine is being used more frequently in elderly patients. Dosing of lamotrigine in elderly patients is based largely on studies from younger adults and not evidence-based data from elderly patients. The goal of this study is to determine the pharmacokinetic parameters, such as clearance, and the factors that have a significant effect on these parameters to provide evidence-based information that can be used to dose elderly patients taking lamotrigine. Lamotrigine plasma concentrations from 148 elderly patients (aged 59-92 years) were used to develop a population pharmacokinetic model. Data were analyzed using NONMEM. Model evaluation was performed using the bootstrap approach and predictive check. The results showed that the blood urea nitrogen/serum creatinine ratio, weight, and phenytoin use significantly affect apparent clearance of lamotrigine. These results show that clinicians may need to take into account these covariates when dosing lamotrigine in this population.

摘要

拉莫三嗪在老年患者中的使用越来越频繁。老年患者拉莫三嗪的给药主要基于年轻成年人的研究,而非老年患者的循证数据。本研究的目的是确定药代动力学参数,如清除率,以及对这些参数有显著影响的因素,以提供可用于给服用拉莫三嗪的老年患者给药的循证信息。来自148名老年患者(年龄59 - 92岁)的拉莫三嗪血浆浓度用于建立群体药代动力学模型。使用NONMEM对数据进行分析。使用自抽样法和预测检验进行模型评估。结果表明,血尿素氮/血清肌酐比值、体重和苯妥英的使用对拉莫三嗪的表观清除率有显著影响。这些结果表明,临床医生在给该人群使用拉莫三嗪给药时可能需要考虑这些协变量。

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