Harivenkatesh Natarajan, Haribalaji Natarajan, David Darling Chellathai, Kumar C M Prabu
*Department of Pharmacology, All India Institute of Medical Sciences, New Delhi; †Rathimed Speciality Hospital, Chennai; and Departments of ‡Pharmacology, and §Biochemistry, Sri Ramachandra Medical College and Research Institute, Chennai, India.
Clin Neuropharmacol. 2015 Jan-Feb;38(1):1-5. doi: 10.1097/WNF.0000000000000057.
Therapeutic drug monitoring (TDM) helps to optimize the dose of antiepileptic drugs. Only limited information is available about the clinical utility of TDM of antiepileptic drugs in India. Hence, we aimed to study the clinical utility of antiepileptic TDM in a tertiary care hospital in India and to explore the association between the plasma drug levels and the occurrence of breakthrough seizures and drug toxicity.
All patients taking antiepileptic drugs for whom TDM was done from January 2008 to December 2010 were included in the study. All relevant information was obtained from patient medical records. Trough levels were measured for all drugs using chemiluminescence assay. Drug levels were interpreted as within, below, and above the reference range, as recommended by the International League Against Epilepsy guidelines.
Of the 420 samples analyzed during this period, 396 samples were included in this study for analysis. The maximum number of requests was for phenytoin (50%) followed by valproic acid (26%). The most common indication for TDM was dosage adjustment (38%) followed by breakthrough seizures (34%). Among the 135 samples received with breakthrough seizures as indication, more than 50% had drug levels either within or above the reference range. Among the 62 samples referred with clinical symptoms of suspected toxicity, drug levels were above the reference range in only 52% of the samples.
Therapeutic drug monitoring was found to be useful in practice, in tailoring drug dosage in accordance with the needs of individual patient, in distinguishing nonresponders from noncompliants, and in aiding in making critical decisions. However, the "reference range" of these antiepileptic drugs was not reliable in predicting the occurrence of breakthrough seizures and clinical symptoms of suspected drug toxicity.
治疗药物监测（TDM）有助于优化抗癫痫药物的剂量。关于抗癫痫药物TDM在印度的临床应用，目前仅有有限的信息。因此，我们旨在研究印度一家三级医疗中心抗癫痫TDM的临床应用，并探讨血浆药物水平与突破性癫痫发作及药物毒性发生之间的关联。
纳入2008年1月至2010年12月期间接受抗癫痫药物治疗并进行TDM的所有患者。所有相关信息均从患者病历中获取。使用化学发光法测定所有药物的谷浓度。按照国际抗癫痫联盟指南的建议，将药物水平解释为在参考范围内、低于参考范围和高于参考范围。
在此期间分析的420个样本中，本研究纳入了396个样本进行分析。请求量最大的是苯妥英（50%），其次是丙戊酸（26%）。TDM最常见的指征是剂量调整（38%），其次是突破性癫痫发作（34%）。在以突破性癫痫发作为指征接收的135个样本中，超过50%的样本药物水平在参考范围内或高于参考范围。在因疑似毒性临床症状转诊的62个样本中，仅52%的样本药物水平高于参考范围。
发现治疗药物监测在实践中很有用，可根据个体患者的需求调整药物剂量，区分无反应者与不依从者，并有助于做出关键决策。然而，这些抗癫痫药物的“参考范围”在预测突破性癫痫发作的发生和疑似药物毒性的临床症状方面并不可靠。
