舒尼替尼
药代动力学
帕唑帕尼
治疗药物监测
药理学
医学
加药
伊马替尼
药品
指南
酪氨酸激酶抑制剂
肿瘤科
索拉非尼
内科学
癌症
病理
肝细胞癌
髓系白血病
作者
Huixin Yu,Neeltje Steeghs,Cynthia M. Nijenhuis,Jan H.M. Schellens,Jos H. Beijnen,Alwin D. R. Huitema
标识
DOI:10.1007/s40262-014-0137-2
摘要
There is accumulating evidence for potential benefits of therapeutic drug monitoring (TDM) in the treatment of cancer with tyrosine kinase inhibitors (TKIs). Relationships between exposure and response (efficacy/toxicity) have been established for several TKIs. For example, the pharmacokinetic targets for efficacy of imatinib, sunitinib and pazopanib have been defined as trough plasma concentrations (Ctrough) of >1,000, >50 and >20,000 ng/mL for selected indications, respectively. Dose adjustment based on pharmacokinetic targets could therefore increase response rates and duration. Furthermore, with appropriate target concentrations defined, excessive side effects in patients using the current fixed dosing strategy may be prevented. This review provides a practical guideline for TDM for the currently approved TKIs at 28 February 2013. The focus of this article is on the elaboration of exposure and response relationships of TKIs with proposed pharmacokinetic targets, mainly Ctrough, and further on the interpretation of the pharmacokinetic targets with recommendations for dose titrations.
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