Cetirizine: A pharmacokinetic and pharmacodynamic evaluation in children with seasonal allergic rhinitis

Abstract

In a double-blind, randomized, parallel-group 5-week study, cetirizine, 5 mg or 10 mg daily, was ingested by 10 and nine children, respectively. Cetirizine was rapidly absorbed with mean peak cetirizine concentrations of 427.6 ± SD, 144.2 ng/ml. 1.4 ± 1.1 hours after the 5 mg dose, and 978.4 ± 340.6 ng/ml, 0.8 ± 0.4 hours after the 10 mg dose. The dose-independent serum-elimination half-life of cetirizine was 7.1 ± 1.6 hours after cetirizine, 5 mg, and 69 ± 1.6 hours after cetirizine, 10 mg. Urinary excretion of unchanged cetirizine during 24 hours after the initial dose of cetirizine, 5 mg, was 40 ± 15%, and after cetirizine, 10 mg, it was 39 ± 14%. The mean histamine-induced wheal-and-flare areas were significantly suppressed from 1 to 24 hours after the first dose of cetirizine, 5 mg, and from $\text{1}\text{2}$ to 24 hours after the first dose of cetirizine, 10 mg, compared to the mean predose wheal-and-flare areas (p < 0.01). During daily dosing with cetirizine, 5 mg or 10 mg at bedtime for 35 days, serum cetirizine concentrations and suppression of histamine-induced wheals and flares were monitored every 7 days, 12 hours after the cetirizine dose. The mean serum cetirizine concentrations remained relatively stable during this time, and the mean wheal-and-flare areas remained significantly suppressed (p < 0.01) compared to baseline wheal-and-flare areas measured before the first dose of cetirizine. The symptoms and signs of allergic rhinitis were suppressed throughout the study by cetirizine, 5 mg and 10 mg. No sedation, dry mouth, or other adverse effects were reported at any time. Cetirizine is a potent, new H₁-receptor antagonist without central nervous system or anticholinergic activity. No evidence of subsensitivity to cetirizine was found during 5 weeks of treatment.