Pharmacology and Therapeutics Unit, Department of Clinical and Experimental Epilepsy, UCL-Institute of Neurology, London, United Kingdom.
Ther Drug Monit. 2013 Feb;35(1):4-29. doi: 10.1097/FTD.0b013e31827c11e7.
Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy. Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM. The advantages of saliva include the fact that for many AEDs it reflects the free (pharmacologically active) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly. For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum. Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting. Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide. Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent.
血液（血清/血浆）抗癫痫药物（AED）治疗药物监测（TDM）已被证明是一种非常有价值的替代标志物，可以用于个体化和优化癫痫患者的药物管理。自 1989 年以来，AED 的数量呈指数级增长，目前已有 23 种获准用于临床，最近，人们对唾液作为替代 AED TDM 基质的应用重新产生了浓厚的兴趣。唾液的优点包括：对于许多 AED 来说，它反映了血清中的游离（药理活性）浓度；易于采样，可以重复采样，采样是非侵入性的；不需要采血技术人员的专业知识；并且许多患者，特别是儿童和老年人更喜欢使用唾液。对于每种 AED，本文综述总结了与 TDM 实践相关的关键药代动力学特征，讨论了其他生物基质的使用，特别是唾液，并探讨了唾液浓度反映血清浓度的证据。还讨论了唾液 AED TDM 的适应证、进行唾液采样时需要考虑的关键因素，最后，描述了一个实用的方案，以便在临床环境中优化应用 AED TDM。总的来说，有令人信服的证据表明，唾液 TDM 可以有效地应用于优化卡马西平、氯巴占、乙琥胺、加巴喷丁、拉科酰胺、左乙拉西坦、奥卡西平、苯巴比妥、苯妥英、苯琥胺、托吡酯和唑尼沙胺的治疗。唾液 TDM 对丙戊酸可能没有帮助，而对于氯硝西泮、依佐加滨、非尔氨酯、普瑞巴林、雷替加滨、鲁非酰胺、司替戊醇、噻加宾和维加特林，数据稀疏或不存在。
