Desloratadine has no clinically relevant electrocardiographic or pharmacodynamic interactions with ketoconazole.
OBJECTIVE
This study was performed to assess the electrocardiographic safety and pharmacokinetics of desloratadine in combination with the CYP3A4 inhibitor ketoconazole.


METHODS
A randomised, placebo-controlled, third-party-blind, 2-way crossover study.


METHODS
24 healthy volunteers (12 men, 12 women; age 19 to 50 years).


METHODS
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.


METHODS
ECG parameters.


RESULTS
Comparable maximum corrected QT (QT(c)) 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 QT(c), 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 (C(max)) 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.


CONCLUSIONS
Coadministration of desloratadine and ketoconazole was well tolerated and was associated with minimal increase in AUC and C(max). The combination did not induce any clinically relevant electrocardiographic changes.
Banfield
Christopher
C
Department of Clinical Pharmacology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539, USA.
Herron
Jerry
J
Keung
Anther
A
Padhi
Desmond
D
Affrime
Melton
M
D000328:Adult; D000704:Analysis of Variance; D000935:Antifungal Agents / Q000009:adverse effects / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007654:Ketoconazole / Q000009:adverse effects / Q000494:pharmacology*; D017336:Loratadine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged
D000935:Antifungal Agents; D006634:Histamine H1 Antagonists; D017336:Loratadine; C121345:desloratadine; D007654:Ketoconazole