Levocetirizine in 1-2 year old children: pharmacokinetic and pharmacodynamic profile.
BACKGROUND
Levocetirizine is an antihistamine with high affinity and selectivity for H1-receptors, which exhibits an excellent benefit/risk ratio in the treatment of allergic rhinitis and urticaria. This is the first study performed with this drug in very young children.


OBJECTIVE
The aim of this study was to confirm the intended regimen of levocetirizine (0.125 mg/kg twice a day) for further studies in children aged 12-24 months.


METHODS
The pharmacokinetic/pharmacodynamic profile of levocetirizine was studied in 15 toddlers suffering from recurrent cough and other allergy-related symptoms, aged 20.7 +/- 3.7 months, and treated twice a day with 0.125 mg/kg for 90 days. A histamine-induced wheal and flare test (W&F) was performed prior to treatment. Blood was sampled at 1, 2, 4, 6, 9 and 12 hours after the first dose. Twelve hours after the evening dose on Days 3-6, and on day 90, a histamine-induced wheal and flare test was repeated and a blood sample was taken for trough value assessment.


RESULTS
A peak plasma level of 286 +/- 68 ng/ml was observed after one hour. The elimination half-life was 4.1 +/- 0.7 hours, the apparent body clearance 1.05 +/- 0.10 ml/min/kg, and the apparent volume of distribution 0.37 +/- 0.06 l/kg. Morning trough values at Days 3-6, and at Day 90 were respectively 78 +/- 30 ng/ml and 110 +/- 86 ng/ml. The median inhibition of the wheal was 100% at Days 3-6, and Day 90. That of the flare was 99.6% at Days 3-6, and 98.9% at Day 90. The overall safety profile of this three-month open study was good.


CONCLUSIONS
This first study with levocetirizine in children aged 12-24 months shows the adequate pharmacokinetic/pharmacodynamic profile and the good safety profile of 0.125 mg/kg levocetirizine given twice a day, which can be proposed for further studies in this age group.
Cranswick
N
N
Royal Children's Hospital and Murdoch Children's Research Institute, University of Melbourne, Australia.
Turzíkova
J
J
Fuchs
M
M
Hulhoven
R
R
D000367:Age Factors; D017332:Cetirizine / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D003371:Cough / Q000188:drug therapy / Q000276:immunology; D005260:Female; D039563:Histamine H1 Antagonists, Non-Sedating / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D012008:Recurrence; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000188:drug therapy*; D012135:Respiratory Sounds / Q000187:drug effects / Q000276:immunology; D014581:Urticaria / Q000188:drug therapy / Q000276:immunology
D039563:Histamine H1 Antagonists, Non-Sedating; D010879:Piperazines; C472067:levocetirizine; D017332:Cetirizine