Influence of itraconazole on the pharmacokinetics and electrocardiographic effects of astemizole

Br J Clin Pharmacol. 1997 Mar;43(3):319-22. doi: 10.1046/j.1365-2125.1997.00548.x.


Aims: The aim of this study was to investigate the influence of chronic itraconazole treatment on the pharmacokinetics and cardiovascular effects of single dose astemizole in healthy subjects was studied.

Methods: Twelve male volunteers were taking orally 200 mg twice daily itraconazole or placebo for 14 days with a washout period of 4 weeks in between. Approximately 2 h after the morning dose of itraconazole or placebo on day 11, 10 mg astemizole was orally administered. The plasma concentrations of astemizole and desmethylastemizole were measured by radioimmunoassay up to 504 h after administration; electrocardiograms with analysis of the QTc interval were recorded up to 24 h post administration.

Results: Itraconazole treatment did not significantly change the peak concentration of astemizole (0.74 vs 0.81 ng ml-1) but it increased the area under the curve from 0 to 24 h (5.46 to 9.95 ng ml-1 h) and from 0 to infinity (17.4 to 48.2 ng ml-1 h), and the elimination half-life (2.1 to 3.6 days). The systemic bioavailability of desmethylastemizole was also increased. The QTc interval did not increase after astemizole administration and there was no difference in the QTc intervals between the itraconazole and placebo session.

Conclusions: Chronic administration of itraconazole influences the metabolism of single dose astemizole in normal volunteers without changes of cardiac repolarization during the first 24 h after astemizole administration. However, the reduction in astemizole clearance under concomitant administration of itraconazole may result in a marked increase in astemizole plasma concentrations and QTc alterations during chronic combined intake of astemizole with itraconazole.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Analysis of Variance
  • Antifungal Agents / pharmacology*
  • Astemizole / pharmacokinetics*
  • Astemizole / pharmacology
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Electrocardiography / drug effects
  • Heart Rate / drug effects
  • Histamine H1 Antagonists / pharmacokinetics*
  • Histamine H1 Antagonists / pharmacology
  • Humans
  • Itraconazole / pharmacology*
  • Linear Models
  • Male


  • Antifungal Agents
  • Histamine H1 Antagonists
  • Itraconazole
  • Astemizole