Patsalos Philip N, Berry David J, Bourgeois Blaise F D, Cloyd James C, Glauser Tracy A, Johannessen Svein I, Leppik Ilo E, Tomson Torbjörn, Perucca Emilio
Institute of Neurology/The National Hospital for Neurology and Neurosurgery, London and The Chalfont Centre for Epilepsy, Chalfont St Peter, United Kingdom.
Epilepsia. 2008 Jul;49(7):1239-76. doi: 10.1111/j.1528-1167.2008.01561.x.
Although no randomized studies have demonstrated a positive impact of therapeutic drug monitoring (TDM) on clinical outcome in epilepsy, evidence from nonrandomized studies and everyday clinical experience does indicate that measuring serum concentrations of old and new generation antiepileptic drugs (AEDs) can have a valuable role in guiding patient management provided that concentrations are measured with a clear indication and are interpreted critically, taking into account the whole clinical context. Situations in which AED measurements are most likely to be of benefit include (1) when a person has attained the desired clinical outcome, to establish an individual therapeutic concentration which can be used at subsequent times to assess potential causes for a change in drug response; (2) as an aid in the diagnosis of clinical toxicity; (3) to assess compliance, particularly in patients with uncontrolled seizures or breakthrough seizures; (4) to guide dosage adjustment in situations associated with increased pharmacokinetic variability (e.g., children, the elderly, patients with associated diseases, drug formulation changes); (5) when a potentially important pharmacokinetic change is anticipated (e.g., in pregnancy, or when an interacting drug is added or removed); (6) to guide dose adjustments for AEDs with dose-dependent pharmacokinetics, particularly phenytoin.
虽然尚无随机研究证明治疗药物监测(TDM)对癫痫临床结局有积极影响,但非随机研究和日常临床经验的证据确实表明,测定新一代和老一代抗癫痫药物(AED)的血清浓度在指导患者管理方面可发挥重要作用,前提是测定浓度时有明确指征,并结合整个临床背景进行审慎解读。AED测量最可能有益的情况包括:(1)当患者已达到理想的临床结局时,确定个体治疗浓度,以便后续用于评估药物反应变化的潜在原因;(2)辅助诊断临床毒性;(3)评估依从性,尤其是在癫痫发作未得到控制或出现突破性发作的患者中;(4)在药代动力学变异性增加的情况下(如儿童、老年人、患有相关疾病的患者、药物剂型改变)指导剂量调整;(5)预期有潜在重要药代动力学变化时(如妊娠期间,或添加或停用相互作用药物时);(6)指导具有剂量依赖性药代动力学的AED的剂量调整,尤其是苯妥英。