Toxicity patterns of cytotoxic drugs
Toxicity patterns of cytotoxic drugs
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DOI：
10.1023/a:1023565227808
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发表时间：
2003-05-01
影响因子：
3.4
通讯作者：
Canal, P
中科院分区：
文献类型：
--
作者：
Chatelut, E;Delord, JP;Canal, P
毒性是抗癌药物的一个主要问题。这些化合物的治疗指数很窄，抗肿瘤效果所需的剂量与导致不可接受的毒性的剂量之间存在微小差异。它们的推荐剂量是根据毒性终点确定的。此外，毒性先于疗效被观察到，因此，毒性效应是细胞毒药物药效学研究的主要终点。在对这些研究的数据进行建模之前，需要了解抗癌药物的毒性模式和主要毒性因素。血液学毒性是细胞毒的主要毒性。然而，在某些情况下，非血液毒性已经变得比血液毒性更重要，作为药效终点，例如与骨髓移植相关的大剂量化疗。本文将介绍细胞毒药物的主要毒性及其患者间和患者内变异性的因素。以拓扑替康的毒性模式为例进行研究。了解一种药物的毒性模式是建立其药效学模型的前提条件。
Toxicity is a major concern for anticancer drugs. These compounds present a narrow therapeutic index, with a small difference between the dose required for an antitumor effect and that responsible for unacceptable toxicity. Their recommended doses are determined according to the toxicity endpoint. Moreover, toxicity is observed earlier than the therapeutic effect, so, toxic effects represent a major endpoint for pharmacodynamic studies of cytotoxic drugs. Knowledge of toxicity patterns and main factors of toxicity of anticancer drugs is required before modeling data of these studies. Hematological toxicities represent the main toxicity of the cytotoxic. However, non-hematological toxicities have become more important than hematological toxicities as pharmacodynamic endpoints in some circumstances such as high-dose chemotherapy associated with bone marrow transplantation. This paper will describe the main toxicity of the cytotoxic drugs, and its factors of both inter- and intra-patient variability. The toxicity pattern of topotecan will be examined as an example. Knowledge of the toxicity pattern of a drug consitutes a prerequirement before modeling its pharmacodynamics.