Objective: This study was performed to assess the electrocardiographic safety and pharmacokinetics of desloratadine in combination with the CYP3A4 inhibitor ketoconazole.
Design: A randomised, placebo-controlled, third-party—blind, 2-way crossover study.
Participants: 24 healthy volunteers (12 men, 12 women; age 19 to 50 years).
Interventions: 7.5mg of desloratadine orally per day in combination with placebo or with 200mg of ketoconazole every 12 hours for 10 days. After a minimum 7-day washout period, participants received the alternative treatment.
Main outcome measures: ECG parameters.
Results: Comparable maximum corrected QT (QTc) intervals were observed after coadministration of desloratadine and placebo or ketoconazole (431 and 435 msec, respectively). The desloratadine/ketoconazole combination did not induce any statistically significant or clinically relevant changes in QTc, QT, PR or QRS intervals compared with desloratadine alone; ventricular rate was slightly slower when desloratadine was given with ketoconazole. At steady state, coadministration of ketoconazole resulted in no significant change in area under the desloratadine concentration-time curve (AUC) from 0 to 24 hours compared with desloratadine/placebo. Coadministration of desloratadine and ketoconazole resulted in a 1.3-fold increase in desloratadine maximum concentration (Cmax) that was not clinically relevant. The most common adverse event was headache, reported in 42 and 38% of individuals, respectively, after coadministration of desloratadine/placebo and desloratadine/ketoconazole. There were no reports of dizziness or syncope.
Conclusion: Coadministration of desloratadine and ketoconazole was well tolerated and was associated with minimal increase in AUC and Cmax. The combination did not induce any clinically relevant electrocardiographic changes.