Pharmacokinetic Study of Levetiracetam in Children

• Published in: Epilepsia (Copenhagen) Vol. 42; no. 12; pp. 1574 - 1579
• Main Authors: Pellock, John M., Glauser, Tracy A., Bebin, E. Martina, Fountain, Nathan B., Ritter, Frank J., Coupez, René M., Shields, W. Donald
• Format: Journal Article
• Language: English
• Published: Boston, MA, USA Blackwell Science Inc 01.12.2001; Blackwell
• Subjects: Adult; Age Factors; Anticonvulsants - pharmacokinetics; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Child; Creatine - metabolism; Epilepsy; Epilepsy - drug therapy; Epilepsy - metabolism; Female; Humans; Keppra; Levetiracetam; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Neuropharmacology; Pediatric; Pharmacokinetics; Pharmacology. Drug treatments; Piracetam - analogs & derivatives; Piracetam - pharmacokinetics; Piracetam - therapeutic use; ucb L057; Human; Nervous system diseases; Metabolite; Epilepsy; Multicenter study; Anticonvulsant; Clearance; Metabolism; Cerebral disorder; Chemotherapy; Treatment; Partial; Central nervous system disease; Pharmacokinetics; Child; Levetiracetam
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1046/j.1528-1157.2001.41300.x

Purpose: The pharmacokinetics of the novel antiepileptic drug (AED) levetiracetam and its major metabolite, ucb L057, were studied in children with partial seizures in a multicenter, open‐label, single‐dose study. Methods: Twenty‐four children (15 boys, nine girls), 6 to 12 years old, received a single dose of levetiracetam (20 mg/kg) as an adjunct to their stable regimen of a single concomitant AED, followed by a 24‐h pharmacokinetic evaluation. Results: In children, the half‐lives of levetiracetam and its metabolite ucb L057 were 6.0 ± 1.1 and 8.1 ± 2.7 hours, respectively. The Cmax and area under the curve (AUC) of levetiracetam equated for a 1‐mg/kg dose were lower in children (Cmax, norm = 1.33 ± 0.35 μg/ml; AUCnorm = 12.4 ± 3.5 μg/h/ml) than in adults (Cmax, norm = 1.38 ± 0.05 μg/ml; AUCnorm = 11.48 ± 0.63 μg/h/ml), whereas the renal clearance was higher. The apparent body clearance (1.43 ± 0.36 ml/min/kg) was ∼30–40% higher in children than in adults. Levetiracetam was generally well tolerated. Conclusions: On the basis of these data, a daily maintenance dose equivalent to 130–140% of the usual daily adult maintenance dosage (1,000–3,000 mg/day) in two divided doses, on a weight‐normalized level (mg/kg/day) is initially recommended. Clinical efficacy trials in children are ongoing with dosages of 20 to 60 mg/kg/day.