The pharmacokinetic and pharmacodynamic interaction between zileuton and terfenadine

Eur J Clin Pharmacol. 1997;52(1):49-54. doi: 10.1007/s002280050248.


Objectives: The effects of zileuton on terfenadine pharmacokinetics, and the effects of terfenadine alone and the combination on the duration of the QTc interval and the morphology of the TU complex were examined.

Methods: The study was double-blind, randomized, placebo-controlled, two period cross-over in 16 healthy volunteers. During each period, subjects received 60 mg of terfenadine every 12 h on days 1 to 7 and 600 mg of either zileuton or placebo for zileuton every 6 h on days 1 to 10. Blood samples were obtained on days 7 to 10 and serial ECGs were performed on days -1 and 7 in both periods.

Results: The combination of zileuton and terfenadine was well tolerated. Coadministration of zileuton with terfenadine resulted in a significant increase in the mean AUC and Cmax of terfenadine by approximately 35% and the mean AUC and Cmax of carboxyterfenadine by approximately 15%. The maximum concentration of terfenadine observed in the study was 9.6 The addition of zileuton to terfenadine did not result in significant changes in the evaluated ECG-recordings (QTc interval and morphology of TU complex). The difference in means for both maximum and average QTc interval was very small (< or = 2.3 ms), and there were no clinically significant changes in individual values.

Conclusions: The relatively small pharmacokinetic effect of zileuton on terfenadine metabolism, with no change in the QTc interval, is unlikely to be of clinical significance. The interaction is minimal in comparison to the background variability of the population.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analysis of Variance
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Synergism
  • Electrocardiography / drug effects
  • Histamine H1 Antagonists / pharmacokinetics*
  • Humans
  • Hydroxyurea / analogs & derivatives*
  • Hydroxyurea / pharmacokinetics
  • Hydroxyurea / pharmacology
  • Lipoxygenase Inhibitors / pharmacokinetics
  • Lipoxygenase Inhibitors / pharmacology*
  • Male
  • Terfenadine / analogs & derivatives
  • Terfenadine / pharmacokinetics
  • Terfenadine / pharmacology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Histamine H1 Antagonists
  • Lipoxygenase Inhibitors
  • Terfenadine
  • zileuton
  • Hydroxyurea