Pharmacokinetics of levetiracetam in infants and young children with epilepsy.
OBJECTIVE
To assess the single-dose pharmacokinetics of levetiracetam and its major metabolite ucb L057 in infants and young children with epilepsy.


METHODS
Eligible patients with a stable regimen of antiepileptic medications received a single oral dose of levetiracetam 20 mg/kg administered as a 10% oral solution followed by a 24-hour pharmacokinetic evaluation.


RESULTS
Thirteen subjects (age 2.3-46.2 months) enrolled and received levetiracetam; 12 provided evaluable pharmacokinetic data. Levetiracetam was rapidly absorbed and reached peak plasma concentration (t(max)) 1.4 +/- 0.9 hours after dosing. The mean half-life (t(1/2)) of levetiracetam was 5.3 +/- 1.3 hours, and the apparent clearance was 1.46 +/- 0.42 mL/min/kg. Graphical differences were observed among three age subgroups (1 to <6 months, 6 to <24 months, and 24 to <48 months); however, statistical analysis was limited due to each subgroup's small sample size. No significant gender differences were detected. Treatment-emergent adverse events were seen in three patients (23.1%) but were not considered to be related to levetiracetam.


CONCLUSIONS
The mean t(1/2) of levetiracetam was shorter and its apparent clearance was more rapid for infants and young children than that previously reported for adults. When determining dosage, age-dependent drug clearance should be considered; these findings suggest that a larger dose of levetiracetam (corrected for body weight) needs to be considered for infants and young children with epilepsy than that given to adults with epilepsy. A single dose of levetiracetam was well tolerated in this study population.
Glauser
Tracy A
TA
Children's Hospital Medical Center, Department of Neurology, Cincinnati, Ohio 45229, USA. tracy.glauser@cchmc.org
Mitchell
Wendy G
WG
Weinstock
Arie
A
Bebin
Martina
M
Chen
Dion
D
Coupez
Rene
R
Stockis
Armel
A
Lu
Zhihong Sarah
ZS
D000284:Administration, Oral; D000367:Age Factors; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam