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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 1/2002

01-11-2002 | Original Research Article

Desloratadine Has No Clinically Relevant Electrocardiographic or Pharmacodynamic Interactions with Ketoconazole

Authors: Christopher Banfield, PhD, Jerry Herron, Anther Keung, Desmond Padhi, Melton Affrime

Published in: Clinical Pharmacokinetics | Special Issue 1/2002

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Abstract

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.
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Metadata
Title
Desloratadine Has No Clinically Relevant Electrocardiographic or Pharmacodynamic Interactions with Ketoconazole
Authors
Christopher Banfield, PhD
Jerry Herron
Anther Keung
Desmond Padhi
Melton Affrime
Publication date
01-11-2002
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue Special Issue 1/2002
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200241001-00006

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