Effects of three XXXX on QT interval in healthy adults after single doses.

@entity3477 @entity2177 @entity2887 @entity972 @entity1162 @entity800
OBJECTIVE: A clinical trial was conducted in healthy adult volunteers to assess the effect of @entity800 , @entity3477 , and @entity2177 on the @entity1162 . METHODS: Electrocardiograms were recorded 24 hours before and after subjects took placebo, 1000 mg @entity800 , 800 mg @entity3477 , and 1500 mg @entity2177 in a double-blind, randomized, 4-period, 4-treatment, 4-sequence crossover trial. Changes in @entity1162 from baseline were assessed by several different methods. RESULTS: Increases in @entity1162 compared with placebo were consistently greater after @entity3477 compared with either @entity800 or @entity2177 . The mean postdose change from baseline QTc (Bazett) intervals for the 24-hour period after treatment with @entity3477 ranged from 16.34 to 17.83 ms (P < .001, compared with placebo). For @entity800 , this change ranged from 3.53 to 4.88 ms (P < .05, compared with placebo), and for @entity2177 , this change ranged from 2.27 to 4.93 ms (P < .05, compared with placebo, with the use of 3 of 5 baseline methods). CONCLUSIONS: A change in QTc (Bazett) interval from baseline can be demonstrated safely in healthy volunteers after single high doses of @entity2887 that achieve approximately 1.5 times the maximum plasma drug concentration that occurs after recommended doses. There is substantial daily variation in both @entity1162 , and the magnitude and frequency of changes in QTc interval can depend on the methods used. These factors need to be considered because clinical trials measuring the effects of drugs on QT intervals are used to estimate the risk of using these drugs. Greater changes in QT and QTc intervals after treatment with @entity3477 compared with @entity800 or @entity2177 are consistent with in vitro observations related to the effect of these drugs on rapid @entity972 (IK(r)) channels. The clinical relevance of these differences is not known.
