OBJECTIVE: To evaluate the bioavailability, cardiac safety and tolerability of desloratadine when given in combination with the CYP3A4 inhibitor erythromycin. DESIGN: A randomised, 2-way crossover, placebo-controlled, third party-blind, multiple dose study. PARTICIPANTS: 24 healthy volunteers (12 men, 12 women) aged 19 to 46 years. INTERVENTIONS:Oral desloratadine 7.5mg daily in combination with either placebo (n = 24) or erythromycin 500mg every 8 hours (n = 24) for 10 days. After a minimum 7-day washout period, participants crossed over to the alternative regimen. MAIN OUTCOME MEASURES: ECG parameters. RESULTS:Desloratadine/erythromycin did not induce clinically or statistically significant changes in any ECG parameter. The maximum corrected QT (QT(c)) interval was 445 msec for both treatments. The peak plasma concentration and area under the plasma concentration-time curve from 0 to 24 hours of desloratadine were slightly increased by 1.2- and 1.1-fold by concomitant administration of erythromycin compared with desloratadine/placebo. Gastrointestinal adverse events were more frequent after desloratadine/erythromycin than desloratadine/placebo (46 vs 4%), reflecting the poor gastrointestinal tolerability of erythromycin. There were no reports of syncope. CONCLUSION: Combined desloratadine/erythromycin therapy was well tolerated and had no clinically relevant electrocardiographic effects at a dose that was 50% higher than the recommended dose of 5mg. Although coadministration of erythromycin slightly increased plasma concentrations of desloratadine, this change did not correlate with any prolongation of the QT(c) interval, and no toxicity was observed clinically.
RCT Entities:
OBJECTIVE: To evaluate the bioavailability, cardiac safety and tolerability of desloratadine when given in combination with the CYP3A4 inhibitor erythromycin. DESIGN: A randomised, 2-way crossover, placebo-controlled, third party-blind, multiple dose study. PARTICIPANTS: 24 healthy volunteers (12 men, 12 women) aged 19 to 46 years. INTERVENTIONS: Oral desloratadine 7.5mg daily in combination with either placebo (n = 24) or erythromycin 500mg every 8 hours (n = 24) for 10 days. After a minimum 7-day washout period, participants crossed over to the alternative regimen. MAIN OUTCOME MEASURES: ECG parameters. RESULTS:Desloratadine/erythromycin did not induce clinically or statistically significant changes in any ECG parameter. The maximum corrected QT (QT(c)) interval was 445 msec for both treatments. The peak plasma concentration and area under the plasma concentration-time curve from 0 to 24 hours of desloratadine were slightly increased by 1.2- and 1.1-fold by concomitant administration of erythromycin compared with desloratadine/placebo. Gastrointestinal adverse events were more frequent after desloratadine/erythromycin than desloratadine/placebo (46 vs 4%), reflecting the poor gastrointestinal tolerability of erythromycin. There were no reports of syncope. CONCLUSION: Combined desloratadine/erythromycin therapy was well tolerated and had no clinically relevant electrocardiographic effects at a dose that was 50% higher than the recommended dose of 5mg. Although coadministration of erythromycin slightly increased plasma concentrations of desloratadine, this change did not correlate with any prolongation of the QT(c) interval, and no toxicity was observed clinically.
Authors: Mathieu S Bolhuis; Prashant N Panday; Arianna D Pranger; Jos G W Kosterink; Jan-Willem C Alffenaar Journal: Pharmaceutics Date: 2011-11-18 Impact factor: 6.321