Jaquenoud Sirot Eveline, van der Velden Jan Willem, Rentsch Katharina, Eap Chin B, Baumann Pierre
Psychiatrische Dienste Aargau AG, MediQ, Klinik Königsfelden, Brugg, Switzerland.
Drug Saf. 2006;29(9):735-68. doi: 10.2165/00002018-200629090-00001.
Therapeutic drug monitoring (TDM) and pharmacogenetic tests play a major role in minimising adverse drug reactions and enhancing optimal therapeutic response. The response to medication varies greatly between individuals, according to genetic constitution, age, sex, co-morbidities, environmental factors including diet and lifestyle (e.g. smoking and alcohol intake), and drug-related factors such as pharmacokinetic or pharmacodynamic drug-drug interactions. Most adverse drug reactions are type A reactions, i.e. plasma-level dependent, and represent one of the major causes of hospitalisation, in some cases leading to death. However, they may be avoidable to some extent if pharmacokinetic and pharmacogenetic factors are taken into consideration. This article provides a review of the literature and describes how to apply and interpret TDM and certain pharmacogenetic tests and is illustrated by case reports. An algorithm on the use of TDM and pharmacogenetic tests to help characterise adverse drug reactions is also presented. Although, in the scientific community, differences in drug response are increasingly recognised, there is an urgent need to translate this knowledge into clinical recommendations. Databases on drug-drug interactions and the impact of pharmacogenetic polymorphisms and adverse drug reaction information systems will be helpful to guide clinicians in individualised treatment choices.
治疗药物监测（TDM）和药物遗传学检测在最大程度减少药物不良反应及增强最佳治疗反应方面发挥着重要作用。个体对药物的反应因遗传构成、年龄、性别、合并症、包括饮食和生活方式（如吸烟和饮酒）在内的环境因素以及诸如药代动力学或药效学药物相互作用等与药物相关的因素而有很大差异。大多数药物不良反应为A型反应，即与血浆水平相关，是导致住院的主要原因之一，在某些情况下可导致死亡。然而，如果考虑药代动力学和药物遗传学因素，在一定程度上这些不良反应可能是可以避免的。本文对文献进行了综述，并描述了如何应用和解读TDM及某些药物遗传学检测，并通过病例报告进行说明。还提出了一个关于使用TDM和药物遗传学检测来帮助确定药物不良反应特征的算法。尽管在科学界，药物反应差异越来越受到认可，但迫切需要将这一知识转化为临床建议。药物相互作用数据库以及药物遗传学多态性的影响和药物不良反应信息系统将有助于指导临床医生进行个体化治疗选择。
