Clinical and Laboratory Observation
Pharmacokinetics of Levetiracetam in Neonates with Seizures

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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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Methods

The institutional review boards at Cincinnati Children's Hospital Medical Center and Good Samaritan Hospital approved the protocol and written informed consent was obtained from the legal guardian of all subjects. We prospectively enrolled infants ≤30 days of age and ≥32 weeks gestational age with seizures treated with levetiracetam who were admitted to the neonatal intensive care unit. Exclusion criteria included birth weight <2000 g and known creatinine level ≥2.0 mg/dL. Consent was obtained

Results

A total of 21 infants who received levetiracetam for clinical seizure control, electrographic seizure control, or both were screened for the study from October 2008 to May 2010, and 19 of these infants were enrolled. The two patients who were not enrolled received levetiracetam before consent could be obtained. One subject was excluded because of a laboratory error. Pharmacokinetic data included 54 levetiracetam measurements from 18 subjects. Patient characteristics are summarized in Table I.

Discussion

Levetiracetam pharmacokinetics were different in this population of neonates with seizures than in adults and older children. The half-life is 6 to 8 hours in adults4 and 5 to 7 hours in older children.12, 13 We found the median half-life to be 8.9 hours, as expected on the basis of the lower clearance of levetiracetam in neonates. The volume of distribution (Vd) is 0.5 to 0.7 L/kg in adults14 and 0.6 to 0.7 L/kg in older children.12, 13 The median Vd in our study was 0.89 L/kg. Because

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    Citation Excerpt :

    Levetiracetam is increasingly prescribed for neonatal seizure treatment, despite a lack of safety and efficacy data (Ahmad et al., 2017). Studies of pharmacokinetics suggest a levetiracetam loading dose > 40 mg/kg and a maintenance dose of > 10 mg/kg/dose administered every 8 h is appropriate (Merhar et al., 2011; Sharpe et al., 2012). A single center study of levetiracetam as an add-on treatment for 32 neonates with HIE whose seizures persisted despite phenobarbital reported that a loading dose of 60 mg/kg and maintenance ~ 60 mg/kg/day was efficacious without obvious side effects (Venkatesan et al., 2017).

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Supported by the National Institutes of Health (grants 5T32AR007594-15 to C.S. and 5K24HD050387 and 5U10HD037249 to A.V.). The authors declare no conflicts of interest.

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