Desloratadine has no clinically relevant electrocardiographic or pharmacodynamic interactions with ketoconazole

Clin Pharmacokinet. 2002;41 Suppl 1:37-44. doi: 10.2165/00003088-200241001-00006.

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 (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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Antifungal Agents / adverse effects
  • Antifungal Agents / pharmacology*
  • Area Under Curve
  • Cross-Over Studies
  • Drug Interactions
  • Electrocardiography / drug effects*
  • Female
  • Histamine H1 Antagonists / adverse effects
  • Histamine H1 Antagonists / pharmacokinetics*
  • Histamine H1 Antagonists / pharmacology
  • Humans
  • Ketoconazole / adverse effects
  • Ketoconazole / pharmacology*
  • Loratadine / adverse effects
  • Loratadine / analogs & derivatives
  • Loratadine / pharmacokinetics*
  • Loratadine / pharmacology
  • Male
  • Middle Aged

Substances

  • Antifungal Agents
  • Histamine H1 Antagonists
  • Loratadine
  • desloratadine
  • Ketoconazole