Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy

Wang, Yinghui; Wang, Li; Lu, Wei; Shang, Dewei; Wei, Min-Ji; Wu, Ye

doi:10.1038/aps.2012.57

Cited by 21 publications

(29 citation statements)

References 22 publications

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“…Previous studies analyzing oral LEV in pediatric children using a nonlinear mixed‐effects model suggested that a plasma LEV concentration after oral LEV was best fitted by the one‐compartment linear model and the important covariate affecting the CL and V were WT and enzyme‐inducing AEDs . A recent PK study of IV LEV in 52 children with epilepsy aged 1 month‐16 years also demonstrated dose‐proportional PK of LEV.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Evaluation of Intravenous Levetiracetam in Children With Epilepsy

Kim

Yum

Yeh

et al. 2018

The Journal of Clinical Pharma

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This study aimed to evaluate the safety and tolerability of intravenous (IV) levetiracetam (LEV) as a monotherapy in children aged 1 month-16 years and to explore the pharmacokinetics (PK) of IV LEV and the time to seizure after IV then oral administration of LEV in pediatric children with epilepsy. Children diagnosed with acute unprovoked seizures requiring in-hospital IV LEV administration were included. After administration, the clinical seizure outcomes, side effects, and the Korean-Child Behavior Checklist were monitored and the PK and repeated time to seizure were analyzed via modeling using NONMEM software. Overall, 37 children with epilepsy were enrolled and underwent a PK analysis (median age, 4.6 years; median weight, 18.0 kg). Nine children (24.3%) had seizure recurrence during the follow-up period (median, 3.8 months) and 5 children (13.5%) experienced LEV-associated adverse events such as irritability (n = 2; 5.4%) and somnolence (n = 3; 8.1%). The plasma LEV concentrations after IV LEV were best described by a one-compartment linear PK model. Only body weight was associated with both the clearance and volume of distribution of LEV. The Weibull distribution model described the time to seizure recurrence well; no statistically significant predictor for the time to seizure was identified. Therefore, IV LEV was a well-tolerated and effective alternative in children with acute unprovoked seizures, and models for the PK and time to repeated seizure recurrence after LEV were successfully developed. In particular, the current use of a weight-based IV LEV dosing regimen in pediatric children is practical.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Evaluation of Intravenous Levetiracetam in Children With Epilepsy

Kim

Yum

Yeh

et al. 2018

The Journal of Clinical Pharma

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“…PPK model of LEV in Chinese children aged 0.5–14 years with epilepsy showed body weight was a significant covariate for LEV clearance24). Sharpe and Haas9) noted the clearance in the neonates was modeled as a simple function of postnatal age.…”

Section: Discussionmentioning

confidence: 99%

Experience and pharmacokinetics of Levetiracetam in Korean neonates with neonatal seizures

et al. 2017

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PurposeThe aims of this study were to evaluate the safety and pharmacokinetics of levetiracetam (LEV) in neonates with seizures and to establish a population pharmacokinetics (PPK) model by using the software NONMEM.MethodsA retrospective analysis of 18 neonatal patients with seizures, who were treated with LEV, including 151 serum samples, was performed. The mean loading dose was 20 mg/kg, followed by a mean maintenance dose of 29 mg/kg/day.ResultsSeventeen neonates (94%) had seizure cessation within 1 week and 16 (84%) remained seizure-free at 30 days under the LEV therapy. The mean serum concentration of LEV was 8.7 µg/mL. Eight samples (5%) were found above the therapeutic range. No serious adverse effects were detected. In the PPK analysis for Korean neonates, the half-life was 9.6 hours; clearance, 0.357 L/hr; and volume of distribution, 4.947 L, showing differences from those in adults.ConclusionLEV is a safe and effective option for the treatment of neonatal seizures with careful therapeutic drug monitoring.

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“…The characteristics of each study are summarised in Table 1. Sneck et al [13] enrolled only healthy subjects, Pigeolet et al included both patients and healthy subjects [14], and the other studies were conducted in patients with epilepsy [15][16][17][18][19][20][21][22][23][24][25][26]. Eight of the fourteen studies enrolled paediatric patients [15,17,18,20,21,[24][25][26]; 2 studies were conducted in neonates [18,21], 4 studies in children less than 18 years of age [15,20,25,26], and 2 studies included both children and adults [17,24].…”

Section: Study Characteristicsmentioning

confidence: 99%

A Review of Population Pharmacokinetic Studies of Levetiracetam

Wang

Zhu

et al. 2020

Preprint

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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 identified influencing covariates. Methods: We systematically searched PubMed and Embase databases from inception to June 30, 2020. The information on study designs, target population, model characteristics, and identified covariates were summarised. Moreover, the pharmacokinetic profiles were compared among neonates, children, and adults. Results: A total of 14 studies were included, among which two involved neonates, four involved children, two involved both children and adults, and six involved only adults. The median value of apparent clearance for children (0.074 [range: 0.038 to 0.079] L/h/kg) was higher than that for adults (0.054 [range: 0.039 to 0.061] L/h/kg). Body weight was found to influence the apparent clearance and volume of distribution significantly, whereas renal function influenced the clearance. Likewise, co-administration with enzyme-inducing antiepileptic drugs (such as carbamazepine and phenytoin) increased the drug clearance by 9 to 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.

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Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy

Cited by 21 publications

References 22 publications

Pharmacokinetic and Pharmacodynamic Evaluation of Intravenous Levetiracetam in Children With Epilepsy

Pharmacokinetic and Pharmacodynamic Evaluation of Intravenous Levetiracetam in Children With Epilepsy

Experience and pharmacokinetics of Levetiracetam in Korean neonates with neonatal seizures

A Review of Population Pharmacokinetic Studies of Levetiracetam

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