Pharmacokinetics of levetiracetam in infants and young children with epilepsy
Pharmacokinetics of levetiracetam in infants and young children with epilepsy
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DOI：
10.1111/j.1528-1167.2007.01090.x
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发表时间：
2007-06-01
期刊：
影响因子：
5.6
通讯作者：
Lu, Zhihong
中科院分区：
文献类型：
--
作者：
Glauser, Tracy A.;Mitchell, Wendy G.;Lu, Zhihong
目的：评估左乙拉西坦及其主要代谢产物ucb L057在婴幼儿癫痫患者中的单次给药药代动力学。Methods：接受稳定抗癫痫药物治疗方案的合格患者接受单次口服左乙拉西坦20 mg/kg 10%口服溶液，随后进行24小时药代动力学评估。13例受试者（年龄2.3-46.2个月）入组并接受左乙拉西坦治疗; 12例提供了可评价的药代动力学数据。左乙拉西坦被迅速吸收，并在给药后1.4 +/- 0.9小时达到血浆峰浓度（t（max））。左乙拉西坦的平均半衰期（t（1/2））为5.3 ± 1.3小时，表观清除率为1.46 ± 0.42 mL/min/kg。在三个年龄亚组（1至< 6个月、6至< 24个月和24至< 48个月）中观察到图形差异;然而，由于每个亚组的样本量较小，统计分析有限。没有发现显著的性别差异。治疗后出现的不良事件中看到三名患者（23.1%），但不被认为是相关的左乙拉西坦。结论：左乙拉西坦的平均t（1/2）较短，其明显的清除率是更迅速的婴儿和幼儿比以前报道的成人。在确定剂量时，应考虑年龄依赖性药物清除率;这些结果表明，与成人癫痫相比，婴儿和幼儿癫痫需要考虑更大剂量的左乙拉西坦（根据体重校正）。在该研究人群中，左乙拉西坦单次给药耐受性良好。
Purpose: To assess the single-dose pharmacokinetics of levetiracetam and its major metabolite ucb L057 in infants and young children with epilepsy.Methods: Eligible patients with a stable regimen of antiepileptic medications received a single oral dose of levetiracetam 20 mg/kg administered as a 10% oral solution followed by a 24-hour pharmacokinetic evaluation.Results: Thirteen subjects (age 2.3-46.2 months) enrolled and received levetiracetam; 12 provided evaluable pharmacokinetic data. Levetiracetam was rapidly absorbed and reached peak plasma concentration (t(max)) 1.4 +/- 0.9 hours after dosing. The mean half-life (t(1/2)) of levetiracetam was 5.3 +/- 1.3 hours, and the apparent clearance was 1.46 +/- 0.42 mL/min/kg. Graphical differences were observed among three age subgroups (1 to < 6 months, 6 to < 24 months, and 24 to < 48 months); however, statistical analysis was limited due to each subgroup's small sample size. No significant gender differences were detected. Treatment-emergent adverse events were seen in three patients (23.1%) but were not considered to be related to levetiracetam.Conclusions: The mean t(1/2) of levetiracetam was shorter and its apparent clearance was more rapid for infants and young children than that previously reported for adults. When determining dosage, age-dependent drug clearance should be considered; these findings suggest that a larger dose of levetiracetam (corrected for body weight) needs to be considered for infants and young children with epilepsy than that given to adults with epilepsy. A single dose of levetiracetam was well tolerated in this study population.