Serum concentrations of levetiracetam in epileptic patients:: The influence of dose and co-medication
Serum concentrations of levetiracetam in epileptic patients:: The influence of dose and co-medication
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DOI：
10.1097/00007691-200312000-00007
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发表时间：
2003-12-01
影响因子：
2.5
通讯作者：
Jürgens, U
中科院分区：
文献类型：
--
作者：
May, TW;Rambeck, B;Jürgens, U
左乙拉西坦（LEV）是一种新的抗癫痫药物，被批准作为添加治疗。既往研究表明LEV与其他抗癫痫药物无相关相互作用。本研究的目的是探讨LEV剂量、年龄和合并用药对LEV血清浓度的影响。总共有297名住院患者的363份样本符合纳入标准（例如，谷浓度、可用体重）。仅当患者的合并用药发生变化时，才考虑两次。计算并比较最常见药物组合的LEV血清浓度与LEV剂量/体重[水平与剂量比，LDR，（μ g/mL）/（mg/kg）]的关系。对对数转换数据进行的协方差分析（使用年龄作为协变量）显示，联合用药对LEV血清浓度具有高度显著性（P < 0.001）影响。LEV +苯妥英、LEV +卡马西平、LEV +奥卡西平、LEV +拉莫三嗪、LEV +苯巴比妥钠、LEV单药治疗、LEV +丙戊酸和LEV+丙戊酸+拉莫三嗪的中位LDR分别为0.32、0.32、0.34、0.45、0.46、0.52、0.53和0.54。在与苯妥英钠（P < 0.001）、卡马西平（P < 0.001）和奥卡西平（P < 0.004）联合用药时，LEV的LDR显著低于LEV单药治疗，而与丙戊酸或拉莫三嗪联合用药的患者LEV的IDR与LEV单药治疗的患者LEV的LDR无显著差异（P > 0.05）。包括所有363个样本的回归分析证实，其他药物（例如，苯妥英、卡马西平）降低LEV浓度。除了合并用药外，年龄对LEV清除率有显著影响。在相同的LEV剂量/体重下，儿童的LEV浓度低于成人。与其他研究相反，我们的数据指出其他酶诱导抗癫痫药物（例如，苯妥英、卡马西平）可适度降低LEV血清浓度（20-30%）。然而，我们的观察结果应得到前瞻性药代动力学研究的证实。
Levetiracetam (LEV) is a new antiepileptic drug approved as add-on therapy. Previous studies indicated that LEV has no relevant interactions with other antiepileptic drugs. The aim of this study was to investigate the influence of LEV dose, age, and co-medication on the serum concentration of LEV. In total, 363 samples of 297 inpatients who fulfilled the inclusion criteria (e.g., trough concentration, body weight available) were investigated. A patient was considered twice only if his co-medication had been changed. The LEV serum concentration in relation to LEV dose/body weight [level-to-dose ratio, LDR, (mug/mL)/(mg/kg)] was calculated and compared for the most frequent drug combinations. Analysis of covariance (using age as covariate) carried out on the log-transformed data showed that co-medication had a highly significant (P < 0.001) effect on LEV serum concentrations. The median LDR of LEV was 0.32 for LEV + phenytoin, 0.32 for LEV + carbamazepine, 0.34 LEV + oxcarbazepine, 0.45 for LEV + lamotrigine, 0.46 for LEV + phenobarital, 0.52 for LEV monotherapy, 0.53 for LEV + valproic acid, and 0.54 LEV + valproic acid + lamotrigine. in co-medication with phenytoin (P < 0.001), carbamazepine (P < 0.001), and oxcarbazepine (P < 0.004), the LDR of LEV was significantly lower than it was with LEV monotherapy, whereas the IDR of LEV of patients on co-medication with valproic acid or lamotrigine did not differ significantly from the LDR of LEV of patients on LEV monotherapy (P > 0.05). Regression analysis including all 363 samples confirmed that other drugs (e.g., phenytoin, carbamazepine) lower LEV concentrations. In addition to co-medication, age had a significant effect on clearance of LEV. Children had lower LEV concentrations than adults on the same LEV dose per body weight. in contrast to other studies, our data point out that other enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine) can moderately decrease LEV serum concentrations (by 20-30%). However, our observations should be confirmed by prospective pharmacokinetic studies.