Multiparametric effect: concentration analyses.
Multiparametric effect: concentration analyses.
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DOI：
10.2741/1260
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发表时间：
2004-05
期刊：
影响因子：
--
通讯作者：
R. Sindhi;V. Berry;J. Janosky
中科院分区：
文献类型：
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作者：
R. Sindhi;V. Berry;J. Janosky
免疫抑制剂药物毒性目前与急性排斥反应竞争，作为临床移植中强效新药疗效失败的主要原因。通过荧光成像技术促进了作为临床使用的替代终点的机制药物靶标的开发，所述荧光成像技术测量刺激的（外周血）淋巴细胞应答上的多种细胞因子和细胞表面受体。然而，向移植受体提供定制药物治疗的承诺仍未实现。在这篇简短的综述中，讨论了免疫抑制剂的临床药物浓度与多参数效应相关的计算算法。基于Hill方程，这些药效学建模技术已被用于模拟单药效应、联合方案效应以及对联合方案的个体反应。这些模型的潜在影响明确了临床移植后免疫抑制从业者面临的临床挑战。
Immunosuppressant drug toxicity currently competes with acute rejection, as the major cause of efficacy failure of potent new agents in clinical transplantation. The development of mechanistic drug targets as surrogate endpoints for use in the clinic has been facilitated by fluorescent imaging techniques which measure multiple cytokines and cell surface receptors on stimulated (peripheral blood) lymphocyte responses. However, the promise of delivering customized drug therapy to the transplant recipient remains unfulfilled. In this brief review, computational algorithms that can relate multiparametric effects to clinical drug concentrations of immunosuppressants are discussed. Based on Hill equations, these pharmacodynamic modeling techniques have been used to simulate single-agent effects, combination regimen effects, as well as the individual response to combination regimens. The potential implications of these models crystallize the clinical challenges confronting practitioners of clinical, post-transplant immunosuppression.