Effects of supratherapeutic doses of ebastine and terfenadine on the QT interval.
OBJECTIVE
The objective of this study was to compare the effects of high doses of ebastine with terfenadine and placebo on QTc.


METHODS
Thirty-two subjects were randomly assigned to four treatments (ebastine 60 mg x day(-1), ebastine 100 mg x day(-1), terfenadine 360 mg x day(-1), placebo) administered for 7 days. Serial ECGs were performed at baseline and day 7 of each period. QT interval was analysed using both Bazett (QTcB) and Fridericia (QTcF) corrections.


RESULTS
Ebastine 60 mg (+ 3.7 ms) did not cause a statistically significant change in QTcB compared with placebo (+ 1.4 ms). The mean QTcB for ebastine 100 mg was increased by + 10.3 ms which was significantly greater than placebo but was significantly less (P < 0.05) than with terfenadine 360 mg (+ 18.0 ms). There were no statistically significant differences in QTcF between ebastine 60 mg (-3.2 ms) or ebastine 100 mg (1.5 ms) and placebo (-2.1 ms); although terfenadine caused a 14.1 ms increase which was significantly different from the other three treatments. The increase in QTcB with ebastine most likely resulted from overcorrection of the small drug-induced increase in heart rate.


CONCLUSIONS
Ebastine at doses up to five times the recommended therapeutic dose did not cause clinically relevant changes in QTc interval.
Gillen
M S
MS
Rhône-Poulenc Rorer Pharmaceuticals Inc., Collegeville, PA, USA.
Miller
B
B
Chaikin
P
P
Morganroth
J
J
D000293:Adolescent; D000328:Adult; D002090:Butyrophenones / Q000008:administration & dosage / Q000009:adverse effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects*; D016593:Terfenadine / Q000008:administration & dosage / Q000009:adverse effects*
D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; D016593:Terfenadine; C058249:ebastine