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耐药性癫痫与托吡酯:血浆浓度及癫痫发作频率

Drug-resistant epilepsy and topiramate: Plasma concentration and frequency of epileptic seizures.

作者信息

Marques Fabiana Angelo, Albuquerque Nayara Cristina Perez de, Campos Marília Silveira de Almeida, Freitas-Lima Priscila, Baldoni André Oliveira, Alexandre Júnior Veriano, Sakamoto Américo Ceiki, Oliveira Anderson Rodrigo Moraes de, Pereira Leonardo Régis Leira

机构信息

School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

Department of Chemistry, School of Philosophy, Science and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

出版信息

Clin Exp Pharmacol Physiol. 2018 Jul;45(7):652-658. doi: 10.1111/1440-1681.12923. Epub 2018 Mar 25.

Abstract

Topiramate (TPM) is a second-generation antiepileptic drug (AED), acting on drug-resistant epilepsy. The aim of the study was to evaluate the influence of the dose, use of other AEDs on TPM plasma concentration (C ), and frequency of epileptic seizures. A cross-sectional analytical study was developed with patients aged 18-60 years, for diagnosis of drug-resistant epilepsy, using TPM in monotherapy or associated with other AEDs. The following variables were analyzed: age, frequency of epileptic seizures, pharmacotherapeutic regimen with its respective doses, adherence to medication treatment, and adverse events score. Thirty-seven patients were included, 83.8% of the patients presented C below the therapeutic range. Multiple linear regression estimated that the increase of 1.0 mg/kg/d promoted an increase of 0.68 μg/mL in TPMC , while the use of inducers predicted a reduction of 2.97 μg/mL (P < .001). Multiple Poisson regression predicts that an increase of 1.0 μg/mL in TPMC decreased the patient's chance of presenting seizures, and patients using AED inducers were about ten times more likely to present seizures than those who do not use (P < .001). In addition, for patients using AED inducers with C below the therapeutic range, the mean number of seizures per month was greater than those with C within the therapeutic range. The prescribed dose and the use of AED inducers influence C of TPM, likewise the low C of first-line AEDs and of the adjuvant in the treatment, TPM, as well as low TPM dose seem to affect the control of epileptic seizures.

摘要

托吡酯(TPM)是一种第二代抗癫痫药物(AED),用于治疗耐药性癫痫。本研究的目的是评估剂量、其他AED的使用对TPM血浆浓度(C)以及癫痫发作频率的影响。对年龄在18至60岁的患者进行了一项横断面分析研究,这些患者被诊断为耐药性癫痫,采用TPM单药治疗或与其他AED联合使用。分析了以下变量:年龄、癫痫发作频率、药物治疗方案及其各自剂量、药物治疗依从性和不良事件评分。共纳入37例患者,83.8%的患者C低于治疗范围。多元线性回归估计,每日每千克体重增加1.0 mg可使TPM C增加0.68 μg/mL,而使用诱导剂预计会使TPM C降低2.97 μg/mL(P <.001)。多元泊松回归预测,TPM C每增加1.0 μg/mL可降低患者发作的几率,使用AED诱导剂的患者发作的可能性比未使用者高约10倍(P <.001)。此外,对于C低于治疗范围的使用AED诱导剂的患者,每月癫痫发作的平均次数高于C在治疗范围内的患者。TPM的处方剂量和AED诱导剂的使用会影响TPM的C,同样,一线AED及其辅助治疗药物的低C以及TPM的低剂量似乎也会影响癫痫发作的控制。

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