title: Effects of supratherapeutic doses of ebastine and terfenadine on the QT interval.
abstract: 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.
authors.affiliation: Rhône-Poulenc Rorer Pharmaceuticals Inc., Collegeville, PA, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Gillen
authors.forename: B
authors.initials: B
authors.lastname: Miller
authors.forename: P
authors.initials: P
authors.lastname: Chaikin
authors.forename: J
authors.initials: J
authors.lastname: Morganroth
mesh_terms: 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*
chemical_list: D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; D016593:Terfenadine; C058249:ebastine