Summary: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 C max and area under the curve (AUC) of levetiracetam equated for a 1-mg/kg dose were lower in children (C max, norm ‫ס‬ 1.33 ± 0.35 g/ml; AUC norm ‫ס‬ 12.4 ± 3.5 g/h/ml) than in adults (C max, norm ‫ס‬ 1.38 ± 0.05 g/ml; AUC norm ‫ס‬ 11.48 ± 0.63 g/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.

Summary:Purpose: 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. Treatmentemergent 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.

The primary objective of the present study was to compare the absorption and disposition of levocetirizine, the eutomer of cetirizine, when administered alone (10 mg) or in presence of the distomer. An additional objective was also to investigate the configurational stability of levocetirizine in vivo in humans. The study was performed in a randomized, two-way cross-over, single-dose design with a wash-out phase of 7 days between the two periods. A total of 12 healthy male and 12 healthy female volunteers were included in the study. Bioequivalence can be concluded from the analysis of the pharmacokinetic parameters of levocetirizine when administered alone or as the racemate cetirizine. No chiral inversion occurs in humans when levocetirizine is administered, i.e. there is no formation of the distomer. When comparing the pharmacokinetic characteristics of levocetirizine and the distomer, the apparent volume of distribution of the eutomer is significantly smaller than that of the distomer (0.41 and 0.60 L/kg, respectively). For an H1-antagonist a small distribution volume can be considered as a positive aspect, both in terms of efficacy and safety. Moreover the non-renal clearance of levocetirizine is also significantly lower than that of the distomer (9.70 and 28.70 mL/min, respectively), which constitutes an additional positive aspect particularly as far as metabolism-based drug interactions are concerned. The information collected in the present study on the pharmacokinetics of levocetirizine and the distomer provide additional reasons for eliminating the distomer and developing levocetirizine as an improvement on cetirizine.

In pharmacokinetic studies of hepatic impairment, including all classes of cirrhosis may be more revealing than including only selected classes of liver failure. No dose adjustment of levetiracetam is necessary in patients with mild to moderate liver impairment; however, patients with severe cirrhosis should initially receive only half of the commonly recommended dose.