Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, 200030, People's Republic of China.
Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.
Clin Pharmacokinet. 2021 Mar;60(3):305-318. doi: 10.1007/s40262-020-00963-2. Epub 2021 Jan 15.
Levetiracetam has been widely used as a treatment option for different types of epilepsy in both adults and children. Because of its large between-subject variability, several population pharmacokinetic studies have been performed to identify its pharmacokinetic covariates, and thus facilitate individualised therapy.
The aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore the identified influencing covariates.
We systematically searched the PubMed and Embase databases from inception to 30 June 2020. The information on study designs, target population, model characteristics, and identified covariates was summarised. Moreover, the pharmacokinetic profiles were compared among neonates, children, and adults.
Fourteen studies were included, among which two involved neonates, four involved children, two involved both children and adults, and six involved adults only. The median value of apparent clearance for children (0.074 L/h/kg [range 0.038-0.079]) was higher than that for adults (0.054 L/h/kg [range 0.039-0.061]). Body weight was found to significantly influence the apparent clearance and volume of distribution, whereas renal function influenced the clearance. Likewise, coadministration with enzyme-inducing antiepileptic drugs (such as carbamazepine and phenytoin) increased the drug clearance by 9-22%, whereas coadministration with valproate acid decreased it by 18.8%.
Levetiracetam dose regimen is dependent on the body size and renal function of patients. Further studies are needed to evaluate levetiracetam pharmacokinetics in neonates and pregnant women.
左乙拉西坦已广泛用于治疗成人和儿童的各种类型癫痫。由于其个体间变异性较大，因此已进行了多项群体药代动力学研究，以确定其药代动力学的协变量，从而实现个体化治疗。
本综述旨在提供左乙拉西坦群体药代动力学研究的概述，并探讨已确定的影响协变量。
我们系统地检索了 PubMed 和 Embase 数据库，检索时间截至 2020 年 6 月 30 日。总结了研究设计、目标人群、模型特征和确定的协变量等信息。此外，还比较了新生儿、儿童和成人的药代动力学特征。
纳入了 14 项研究，其中 2 项涉及新生儿，4 项涉及儿童，2 项同时涉及儿童和成人，6 项仅涉及成人。儿童（0.074 L/h/kg [范围 0.038-0.079]）的表观清除率中位数高于成人（0.054 L/h/kg [范围 0.039-0.061]）。体重被发现对表观清除率和分布容积有显著影响，而肾功能则影响清除率。同样，与酶诱导抗癫痫药物（如卡马西平和苯妥英）联合使用会使药物清除率增加 9%-22%，而与丙戊酸合用则会使清除率降低 18.8%。
左乙拉西坦的剂量方案取决于患者的体型和肾功能。需要进一步研究来评估新生儿和孕妇的左乙拉西坦药代动力学。
