The electrocardiographic effects of cetirizine in normal subjects.
OBJECTIVE
To establish whether the antihistamine cetirizine has the potential to prolong the QTc interval in normal volunteers at up to six times the usual recommended dose.


METHODS
Twenty-five healthy volunteers were studied in a prospective, double-blind crossover design conducted on inpatients in a Clinical Research Center. The primary end point of the study was QTc prolongation on the surface electrocardiogram (ECG). Plasma concentrations of cetirizine were also measured for pharmacokinetic analysis. The end point for the pharmacokinetic analysis was the dose/area under the concentration-time curve (apparent clearance of an oral dose). The subjects received the following three treatments in random sequence: placebo, 20 mg/day cetirizine, and 60 mg/day cetirizine for 7 consecutive days. A series of baseline ECGs was recorded over 2 days before each treatment, while the subject receiving placebo. ECG effects of the treatments were then compared with the baseline ECGs.


RESULTS
Analysis of variance showed no difference between the treatment groups (placebo, 20 mg cetirizine, and 60 mg cetirizine every day) in effect on QTc compared with baseline. A paired Student t test showed no difference in dose/area under the concentration-time curve between the 20 mg/day and 60 mg/day dosing groups at steady state.


CONCLUSIONS
In healthy volunteers, cetirizine does not prolong the QTc interval at doses of up to six times the usual recommended dose.
Sale
M E
ME
Department of Medicine, Georgetown University, Washington, DC 20007.
Barbey
J T
JT
Woosley
R L
RL
Edwards
D
D
Yeh
J
J
Thakker
K
K
Chung
M
M
D000328:Adult; D000704:Analysis of Variance; D017332:Cetirizine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012016:Reference Values
D017332:Cetirizine