Levocetirizine: pharmacokinetics and pharmacodynamics in children age 6 to 11 years

BACKGROUND: The pharmacokinetics and pharmacodynamics of medications may differ between children and adults, necessitating different dose regimens for different age groups. Levocetirizine, the active enantiomer of cetirizine, is used in the treatment of allergic rhinitis and chronic urticaria in Europe. Its pharmacokinetics and pharmacodynamics have not yet been studied prospectively in school-age children. OBJECTIVES: This study was performed to investigate levocetirizine pharmacokinetic disposition and pharmacodynamics in relation to skin reactivity to histamine in children aged 6 to 11 years. METHODS: Blood samples were obtained at predose baseline and at defined intervals up to and including 28 hours after a 5-mg levocetirizine dose. Concurrently, epicutaneous tests with histamine phosphate, 1 mg/mL, were performed. Wheals and flares were traced at 10 minutes, and the areas were measured with a computerized digitizing system. RESULTS: In children aged 8.6 +/- 0.4 years (+/- SEM), the peak levocetirizine concentration was 450 +/- 37 ng/mL, and the time at which peak concentrations occurred was 1.2 +/- 0.2 hours. The terminal elimination half-life was 5.7 +/- 0.2 hours, the oral clearance was 0.82 +/- 0.05 mL/min/kg, and the volume of distribution was 0.4 +/- 0.02 L/kg. Compared with predose areas, the wheals and flares produced by histamine phosphate were significantly decreased from 1 to 28 hours, inclusive (P < .05). Mean maximum inhibition of wheals and flares occurred from 2 to 10 hours (97% +/- 1%) and from 2 to 24 hours (93% +/- 1%), respectively. CONCLUSIONS: Levocetirizine had an onset of action within 1 hour and provided significant peripheral antihistaminic activity for 28 hours after a single dose. Once-daily dosing may be optimal in children aged 6 to 11 years, as it is in adults.