Article

Pharmacokinetics of Levetiracetam in Neonates with Seizures

Perinatal Institute, Division of Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
The Journal of pediatrics (Impact Factor: 3.79). 07/2011; 159(1):152-154.e3. DOI: 10.1016/j.jpeds.2011.03.057
Source: PubMed

ABSTRACT

The pharmacokinetics of levetiracetam were determined prospectively in 18 neonates with seizures. Neonates were found to have lower clearance, higher volume of distribution, and a longer half-life as compared with older children and adults. Mild somnolence was the only adverse effect.

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Available from: Catherine Mary Turner Sherwin
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    • "The only adverse effect observed was mild somnolence 24 h after LEV administration. Thus, Merhar and colleagues concluded that the pharmacokinetics of LEV in neonates differed from children and adults (16). "
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    ABSTRACT: Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam (IV LEV), a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of IV LEV and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.
    Full-text · Article · Dec 2013 · Frontiers in Neurology
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    • "The CL/F of this study was lower than in the children in the studies by Toublanc and Chhun17,18. In Merhar's study of neonates24, clearance was 1.21 mL·min−1·kg−1. In Pellock's study12 of 6–12 years old, CL/F was 1.43 mL·min−1·kg−1, which was higher than that in adults (0.96 mL·min−1·kg−1) and than the 0.69 mL·min−1·kg−1 observed in the current study. "
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    ABSTRACT: To establish a population pharmacokinetics (PPK) model of levetiracetam in Chinese children with epilepsy. A total of 418 samples from 361 epileptic children in Peking University First Hospital were analyzed. These patients were divided into two groups: the PPK model group (n=311) and the PPK validation group (n=50). Levetiracetam concentrations were determined by HPLC. The PPK model of levetiracetam was established using NONMEM, according to a one-compartment model with first-order absorption and elimination. To validate the model, the mean prediction error (MPE), mean squared prediction error (MSPE), root mean-squared prediction error (RMSPE), weight residues (WRES), and the 95% confidence intervals (95% CI) were calculated. A regression equation of the basic model of levetiracetam was obtained, with clearance (CL/F)=0.988 L/h, volume of distribution (V/F)=12.3 L, and K(a)=1.95 h(-1). The final model was as follows: K(a)=1.56 h(-1), V/F=12.1 (L), CL/F=1.04×(WEIG/25)(0.583) (L/h). For the basic model, the MPE, MSPE, RMSPE, WRES, and the 95%CI were 9.834 (-0.587-197.720), 50.919 (0.012-1286.429), 1.680 (0.021-34.184), and 0.0621 (-1.100-1.980). For the final model, the MPE, MSPE, RMSPE, WRES, and the 95% CI were 0.199 (-0.369-0.563), 0.002082 (0.00001-0.01054), 0.0293 (0.001-0.110), and 0.153 (-0.030-1.950). A one-compartment model with first-order absorption adequately described the levetiracetam concentrations. Body weight was identified as a significant covariate for levetiracetam clearance in this study. This model will be valuable to facilitate individualized dosage regimens.
    Full-text · Article · Jun 2012 · Acta Pharmacologica Sinica
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    ABSTRACT: INTRODUCTION: In the treatment of epilepsy it is necessary to select drugs with high efficacy and minimum side effects. Levetiracetam seems to have an ideal pharmacological profile. Although the oral route is the usual form of administration, sometimes it is required the intravenous administration. OBJECTIVE: To describe the clinical profile, indications in intravenous administration and seizures control of 48 pediatric epileptic patients managed with intravenous levetiracetam in monotherapy or add-on therapy. METHODS: This is a retrospective and observational study performed at the National Institute of Pediatrics between February 2011 to April 2013, in patients receiving intravenous levetiracetam, for whom the enteral route was contraindicated. RESULTS: A total of 48 records were included, 60% of the population < 2 years. Symptomatic focal epilepsy was present in 39 patients (81%). The most common etiologies were: hypoxic-ischemic encephalopathy (HIE) (n = 14), cerebral dysgenesis (n = 10) and acquired metabolic disorders (n = 7). Indications for intravenous administration: uncontrolled seizures (n = 23) and fasting due to medical illness (n = 11). A total of 43 patients (89.5%) were seizure-free during the first 24 h. Intravenous administration was performed with dose 20 mg/kg b.i.d. and the patients received 2 to 6 IV doses, without any adverse effects. Once the enteral route was restored, the change from intravenous to oral route was made in equivalent doses. In all, 35 patients (73%) maintained levetiracetam treatment in mono/politherapy for up to 36 months (average 18.5 months, SD ± 10.5). A total of 13 patients (27%) discontinued levetiracetam, none for therapeutic failure, 1 patient developed aggression during the first week as adverse event and suspended levetiracetam, followed by economic hardship. CONCLUSIONS: This series shows that levetiracetam is an antiepileptic drug that enabled adequate control in acute seizures and chronic management of epilepsy. Adherence was obtained in 80% of patients. The levetiracetam is a safe, broad-spectrum antiepileptic with few adverse effects and is a good option for intravenous use in children.
    No preview · Article · · Revista Mexicana de Neurociencia
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