Cetirizine: a pharmacokinetic and pharmacodynamic evaluation in children with seasonal allergic rhinitis.
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 6.9 +/- 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 1/2 to 24 hours after the first dose of cetirizine, 10 mg, compared to the mean predose wheal-and-flare areas (p less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Watson
W T
WT
Health Sciences Clinical Research Center, Faculty of Medicine, Winnipeg, Manitoba, Canada.
Simons
K J
KJ
Chen
X Y
XY
Simons
F E
FE
D017332:Cetirizine; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006919:Hydroxyzine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011897:Random Allocation; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy*
D006634:Histamine H1 Antagonists; D006919:Hydroxyzine; D017332:Cetirizine