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


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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    • "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.
    Frontiers in Neurology 12/2013; 4:192. DOI:10.3389/fneur.2013.00192
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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.
    Acta Pharmacologica Sinica 06/2012; 33(6):845-51. DOI:10.1038/aps.2012.57 · 2.91 Impact Factor
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    ABSTRACT: In recent years, several new-generation antiepileptic drugs (AEDs) have been introduced in clinical practice. These agents, which include felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, vigabatrin and zonisamide, are being increasingly used in the treatment of epilepsy at the extremes of age. For a rational prescribing of these drugs in specific age groups, major pharmacokinetic changes that occur during development and aging need to be taken into consideration. A review of available evidence indicates that the apparent oral clearance (CL/F) of new-generation AEDs in children is increased by 20-170% (depending on the type of drug and characteristics of the patients studied) compared with adults, with the highest CL/F values usually being observed in the youngest age groups. These findings do not necessarily apply to the first weeks of life, when drug eliminating capacity is still undergoing maturation, as in the case of lamotrigine for which preliminary data suggest that CL/F in neonates aged <2 months can be much lower than in infants aged 2-12 months. At the other extreme of age, in the elderly, CL/F is almost invariably reduced (on average by 10-50%) compared with values found in non-elderly adults. Age-related CL/F changes, together with the large interindividual pharmacokinetic variability, contribute to the need for individualised dosage requirements in these patients. Measurement of serum drug concentrations can be useful as an aid to dosage individualization in these age groups but interpretation of therapeutic drug monitoring data should also take into account the possibility of age-related changes in pharmacodynamic sensitivity and, for neonates and the elderly, alterations in drug binding to serum proteins.
    Clinical Pharmacokinetics 02/2006; 45(4):351-63. DOI:10.2165/00003088-200645040-00002 · 5.05 Impact Factor
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