Therapeutic drug monitoring of cancer chemotherapy.
Therapeutic drug monitoring of cancer chemotherapy.
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DOI：
10.1177/1078155207081133
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发表时间：
2007-12-01
期刊：
影响因子：
--
通讯作者：
Alnaim, Lamya
中科院分区：
文献类型：
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作者：
Alnaim, Lamya
治疗药物监测不常规用于化疗药物。有几个原因，但一个主要的缺点是缺乏既定的治疗浓度范围。联合化疗使得难以建立单个药物的治疗范围，单个药物的浓度-效应关系可能与该药物在药物组合中使用时的浓度-效应关系不同。许多类别的细胞毒性化合物的药代动力学优化方案存在于专门的中心，其中一些方案现在是大型多中心试验的一部分。尽管如此，TDM显然有潜力改善化疗药物的临床使用，其中大多数药物的治疗指数非常窄，药代动力学变化很大。在过去15年中积累的大量文献证明了全身暴露于各种化疗药物与其毒性或治疗效果之间的关系。本文综述了TDM的概念，除了化疗药物的药代动力学建模的基础上的工具。有时使用先验或后验方法单独调整化疗剂的施用剂量。这些模型只能通过使用与原始研究相同的剂量和时间表来应用。贝叶斯估计在血液采样时间方面提供了更大的灵活性，并且由于其精确性和所提供的信息量，是确保特定患者从所需的全身暴露中受益的首选方法。此外，药物遗传学作为个体化化疗的工具的作用和应用进行了讨论，突出了已被充分研究和定义的药物和机制及其与临床实践的相关性。最后，本文讨论了在临床环境中优化使用TDM的关键问题，以及临床药剂师在这方面的作用。此外，它还讨论了在这一领域的未来发展，可以有助于改善癌症化疗方面的病人的结果和生存。
Therapeutic drug monitoring is not routinely used for chemotherapy agents. There are Several reasons, but one major drawback is the lack of established therapeutic Concentration ranges. Combination chemotherapy makes the establishment of Therapeutic ranges for individual drugs difficult, the concentration-effect relationship for a single drug may not be the same as when that drug is used in a drug combination. Pharmacokinetic optimization protocols for many classes of cytotoxic compounds exist in specialized centers, and some of these protocols are now part of large multicentre trials. Nonetheless, TDM clearly has the potential to improve the clinical use of chemotherapy gents, most of which have very narrow therapeutic indices and highly variable pharmacokinetics. A substantial body of literature accumulating during the past 15 years demonstrates relationships between systemic exposure to various chemotherapy agents and their toxic or therapeutic effects. This article reviews TDM concepts in addition to tools based on pharmacokinetic modeling of chemotherapy agents. The administered dose of chemotherapy agents is sometimes adjusted individually using either a priori or a posteriori methods. These models can only be applied by using the same dose and schedule as the original study. Bayesian estimation offers more flexibility in blood sampling times and, owing to its precision and to the amount of information provided is the method of choice for ensuring that a given patient benefits from the desired systemic exposure. Moreover, the role and application of Pharmacogenetics as a tool for individualizing chemotherapy is discussed highlighting the agents and mechanisms that have been well studied and defined and their relevance to clinical practice. Finally, this paper address issues critical to the optimal use of TDM in a clinical setting, and the role of clinical pharmacist in this regard. In addition, it discusses future developments in this field that can contribute to improving cancer chemotherapy In terms of patient outcome and survival.