Glauser Tracy A, Mitchell Wendy G, Weinstock Arie, Bebin Martina, Chen Dion, Coupez Rene, Stockis Armel, Lu Zhihong Sarah
Children's Hospital Medical Center, Department of Neurology, Cincinnati, Ohio 45229, USA.
Epilepsia. 2007 Jun;48(6):1117-22. doi: 10.1111/j.1528-1167.2007.01090.x. Epub 2007 Apr 18.
To assess the single-dose pharmacokinetics of levetiracetam and its major metabolite ucb L057 in infants and young children with epilepsy.
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.
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.
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.
评估左乙拉西坦及其主要代谢产物ucb L057在癫痫婴幼儿中的单剂量药代动力学。
符合条件且抗癫痫药物治疗方案稳定的患者口服单剂量20 mg/kg左乙拉西坦，以10%口服溶液给药，随后进行24小时药代动力学评估。
13名受试者（年龄2.3 - 46.2个月）入组并接受了左乙拉西坦治疗；12名提供了可评估的药代动力学数据。左乙拉西坦吸收迅速，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）之间观察到图形差异；然而，由于每个亚组样本量小，统计分析受到限制。未检测到显著的性别差异。3名患者（23.1%）出现治疗中出现的不良事件，但不认为与左乙拉西坦有关。
与先前报道的成人相比，癫痫婴幼儿的左乙拉西坦平均t(1/2)较短，表观清除率更快。确定剂量时，应考虑年龄依赖性药物清除率；这些发现表明，与癫痫成人相比，癫痫婴幼儿可能需要更大剂量（按体重校正）的左乙拉西坦。本研究人群对单剂量左乙拉西坦耐受性良好。
