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.


OBJECTIVE
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.
Simons
F Estelle R
FE
Department of Pediatrics and Child Health, Department of Immunology, Canadian Institutes of Health Research National Training Program in Allergy and Asthma, Faculty of Medicine, The University of Mantoba, Manitoba, Canada. lmcniven@hsc.mb.ca
Simons
Keith J
KJ
D017332:Cetirizine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D002648:Child; D005260:Female; D039563:Histamine H1 Antagonists, Non-Sedating / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology
D039563:Histamine H1 Antagonists, Non-Sedating; D010879:Piperazines; C472067:levocetirizine; D017332:Cetirizine