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系统性红斑狼疮治疗的药代动力学建模

Pharmacokinetic modeling of therapies for systemic lupus erythematosus.

作者信息

Yang Xiaoyan, Sherwin Catherine M T, Yu Tian, Yellepeddi Venkata K, Brunner Hermine I, Vinks Alexander A

机构信息

a 1 Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA.

出版信息

Expert Rev Clin Pharmacol. 2015;8(5):587-603. doi: 10.1586/17512433.2015.1059751. Epub 2015 Jul 9.

Abstract

With the increasing use of different types of therapies in treating autoimmune diseases such as systemic lupus erythematosus (SLE), there is a need to utilize pharmacokinetic (PK) strategies to optimize the clinical outcome of these treatments. Various PK analysis approaches, including population PK modeling and physiologically based PK modeling, have been used to evaluate drug PK characteristics and population variability or to predict drug PK profiles in a mechanistic manner. This review outlines the PK modeling of major SLE therapies including immunosuppressants (methotrexate, azathioprine, mycophenolate and cyclophosphamide, among others) and immunomodulators (intravenous immunoglobulin). It summarizes the population PK modeling, physiologically based PK modeling and model-based individualized dosing strategies to improve the therapeutic outcomes in SLE patients.

摘要

随着在治疗系统性红斑狼疮(SLE)等自身免疫性疾病中使用不同类型疗法的情况日益增多,有必要采用药代动力学(PK)策略来优化这些治疗的临床效果。各种PK分析方法,包括群体PK建模和基于生理学的PK建模,已被用于评估药物的PK特性和群体变异性,或以一种机制性的方式预测药物的PK概况。本综述概述了包括免疫抑制剂(如甲氨蝶呤、硫唑嘌呤、霉酚酸酯和环磷酰胺等)和免疫调节剂(静脉注射免疫球蛋白)在内的主要SLE疗法的PK建模。它总结了群体PK建模、基于生理学的PK建模以及基于模型的个体化给药策略,以改善SLE患者的治疗效果。

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