McCudden Christopher R
Department of Pathology and Laboratory Medicine, Division of Biochemistry, University of Ottawa, 501 Smyth Rd., Ottawa, ON K1H 8L6, Canada.
Diagnosis (Berl). 2018 Jun 27;5(2):47-61. doi: 10.1515/dx-2018-0001.
Therapeutic drug monitoring (TDM) is used to manage drugs with a narrow window between effective and toxic concentrations. TDM involves measuring blood concentrations of drugs to ensure effective therapy, avoid toxicity and monitor compliance. Common drugs for which TDM is used include aminoglycosides for infections, anticonvulsants to treat seizures, immunosuppressants for transplant patients and cardiac glycosides to regulate cardiac output and heart rate. An essential element of TDM is the provision of accurate and clinically relevant reference intervals. Unlike most laboratory reference intervals, which are derived from a healthy population, TDM reference intervals need to relate to clinical outcomes in the form of efficacy and toxicity. This makes TDM inherently more difficult to develop as healthy individuals are not on therapy, so there is no "normal value". In addition, many of the aforementioned drugs are old and much of the information regarding reference intervals is based on small trials using methods that have changed. Furthermore, individuals have different pharmacokinetics and drug responses, particularly in the context of combined therapies, which exacerbates the challenge of universal TDM targets. This focused review examines the origins and limitations of existing TDM reference intervals for common drugs, providing targets where possible based on available guidelines.
治疗药物监测（TDM）用于管理有效浓度和毒性浓度区间狭窄的药物。TDM包括测量药物的血药浓度，以确保有效治疗、避免毒性并监测依从性。使用TDM的常见药物包括用于治疗感染的氨基糖苷类、用于治疗癫痫发作的抗惊厥药、用于移植患者的免疫抑制剂以及用于调节心输出量和心率的强心苷。TDM的一个基本要素是提供准确且与临床相关的参考区间。与大多数源自健康人群的实验室参考区间不同，TDM参考区间需要以疗效和毒性的形式与临床结果相关。这使得TDM本质上更难制定，因为健康个体未接受治疗，所以不存在“正常值”。此外，上述许多药物年代久远，关于参考区间的许多信息是基于使用已改变方法的小型试验。此外，个体具有不同的药代动力学和药物反应，特别是在联合治疗的情况下，这加剧了通用TDM靶点的挑战。这篇重点综述探讨了常见药物现有TDM参考区间的起源和局限性，并根据现有指南尽可能提供靶点。
