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癌症患者中非抗癌药物的治疗药物监测

Therapeutic drug monitoring of non-anticancer drugs in cancer patients.

作者信息

Joerger M, Schellens J H M, Beijnen J H

机构信息

Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands.

出版信息

Methods Find Exp Clin Pharmacol. 2004 Sep;26(7):531-45. doi: 10.1358/mf.2004.26.7.863736.

Abstract

Therapeutic drug monitoring (TDM) or the measurement of drug concentrations in plasma, serum or blood, aims to improve clinical activity, avoid toxicity, and reduce the costs of drug treatment. Specific conditions for TDM to be reasonably applied include the availability of a validated assay, a considerable interindividual pharmacokinetic variability, a high correlation between drug concentration and toxicity, and a narrow therapeutic index. Cancer patients are especially prone to drug-drug interactions due to significant comedication, impaired liver and kidney function and hypoalbuminemia with altered drug binding. This article discusses TDM for various broadly used non-anticancer drugs in cancer patients and gives specific recommendations. Selected drugs covered in this article include those regularly used in febrile neutropenic patients such as the glycopeptide antibiotics, aminoglycosides, the antifungal agents, including flucytosine and azole compounds, the anticonvulsants phenytoin, carbamazepine and valproate, the tricyclic antidepressants, selective-serotonin-reuptake inhibitors, lithium, morphine, digitalis glycosides and the immunosupressants cyclosporin A, tacrolimus, sirolimus and mycophenolate mofetil, crucial compounds in the setting of bone marrow transplantation. In all cases, treating physicians have to consider the variability in patient age, disease stage, comedication, organ function and protein level to weigh the pros and cons of TDM in the individual cancer patient.

摘要

治疗药物监测(TDM),即测量血浆、血清或血液中的药物浓度,旨在提高临床疗效、避免毒性反应并降低药物治疗成本。合理应用TDM的特定条件包括具备经过验证的检测方法、个体间药代动力学存在显著差异、药物浓度与毒性之间具有高度相关性以及治疗指数较窄。癌症患者由于合并用药情况严重、肝肾功能受损以及药物结合改变导致的低白蛋白血症,尤其容易发生药物相互作用。本文讨论了癌症患者中各种广泛使用的非抗癌药物的TDM情况并给出了具体建议。本文涵盖的选定药物包括发热性中性粒细胞减少患者常用的药物,如糖肽类抗生素、氨基糖苷类、抗真菌药物(包括氟胞嘧啶和唑类化合物)、抗惊厥药物苯妥英钠、卡马西平和丙戊酸盐、三环类抗抑郁药、选择性5-羟色胺再摄取抑制剂、锂盐、吗啡、洋地黄苷以及免疫抑制剂环孢素A、他克莫司、西罗莫司和霉酚酸酯,这些都是骨髓移植过程中的关键化合物。在所有情况下,治疗医生都必须考虑患者年龄、疾病阶段、合并用药情况、器官功能和蛋白质水平的差异,以权衡TDM对个体癌症患者的利弊。

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