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药代动力学与药效学的整合:理解剂量反应。

The integration of pharmacokinetics and pharmacodynamics: understanding dose-response.

作者信息

Abdel-Rahman Susan M, Kauffman Ralph E

机构信息

Division of Pediatric Clinical Pharmacology and Medical Toxicology, The Children's Mercy Hospital and Clinics, Department of Pediatrics, University of Missouri-Kansas City, Kansas City, Missouri 64108, USA.

出版信息

Annu Rev Pharmacol Toxicol. 2004;44:111-36. doi: 10.1146/annurev.pharmtox.44.101802.121347.

Abstract

Pharmacokinetic (PK) and pharmacodynamic (PD) studies have proven to be powerful and instructive tools, particularly in elucidating important aspects of human pharmacology. Nevertheless, they remain imperfect tools in that they only allow researchers to indirectly extrapolate, through computational modeling, the dynamic processes of drug action. Furthermore, neither tool alone provides a complete nor necessarily relevant picture of drug action. This review explores the utility and applications of PK and PD in the study of drugs, provides examples of lessons learned from their application to studies of human pharmacology, points out some of their limitations, and advances the thesis that these tools ideally should be employed together in an integrated approach. As we continue to apply these tools across the continuum of age and disease, they provide a powerful means to enhance our understanding of drug action, drug interactions, and intrinsic host factors that influence pharmacologic response.

摘要

药代动力学(PK)和药效学(PD)研究已被证明是强大且具指导意义的工具,尤其是在阐明人体药理学的重要方面。然而,它们仍是不完善的工具,因为它们仅允许研究人员通过计算建模间接推断药物作用的动态过程。此外,单独使用这两种工具都无法提供药物作用的完整或必然相关的图景。本综述探讨了PK和PD在药物研究中的效用及应用,提供了从其应用于人体药理学研究中汲取的经验教训的实例,指出了它们的一些局限性,并提出了这些工具理想情况下应以综合方法一起使用的论点。随着我们继续在不同年龄和疾病范围内应用这些工具,它们提供了一种强大的手段,以增强我们对药物作用、药物相互作用以及影响药理反应的内在宿主因素的理解。

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