Zi-Ran Li1,2, Chen-Yu Wang1, Xiao Zhu3, Zheng Jiao4. 1. Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, 200030, People's Republic of China. 2. Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China. 3. School of Pharmacy, University of Otago, Dunedin, New Zealand. 4. Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, 200030, People's Republic of China. jiaozhen@online.sh.cn.
Abstract
BACKGROUND: 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. OBJECTIVE: The aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore the identified influencing covariates. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.
BACKGROUND: 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. OBJECTIVE: The aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore the identified influencing covariates. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.
Authors: Amerins Weijenberg; Jens H J Bos; Catharina C M Schuiling-Veninga; Oebele F Brouwer; Petra M C Callenbach Journal: Epilepsy Res Date: 2018-07-23 Impact factor: 3.045
Authors: Romy Tilen; Paolo Paioni; Aljoscha N Goetschi; Roland Goers; Isabell Seibert; Daniel Müller; Julia A Bielicki; Christoph Berger; Stefanie D Krämer; Henriette E Meyer Zu Schwabedissen Journal: Pharmaceutics Date: 2022-06-17 Impact factor: 6.525