Lack of cytochrome P450 1A2 interaction effect of ABT-761 on the pharmacokinetics of theophylline

Am J Ther. 1998 Sep;5(5):303-6. doi: 10.1097/00045391-199809000-00005.

Abstract

ABT-761 is a second-generation 5-lipoxygenase inhibitor for the treatment of asthma. The effects of ABT-761 on the pharmacokinetics of theophylline were assessed in 15 adult volunteers in a phase I, multiple-dose, open-label, one-period study. Subjects received a single 400-mg dose of theophylline on days 1 and 8 and 200-mg oral doses of ABT-761 once daily beginning on day 3 and continuing through day 9. The pharmacokinetic parameters of theophylline after administration of theophylline alone and concomitantly with ABT-761 were compared using a paired t-test. No statistically significant differences were observed between the pharmacokinetic parameters of theophylline administered alone and theophylline with concomitant administration of ABT-761. The 95% confidence interval for the ratio of the mean with ABT-761 dosing to the mean for theophylline alone was 0.970 to 1.127 for area under the plasma concentration-time curve and 0.887 to 1.036 for maximal plasma concentration. The lack of an inhibition effect by ABT-761 on theophylline clearance suggested that ABT-761 may have a low affinity for the cytochrome P450 1A2 isozyme, the primary isozyme responsible for theophylline metabolism.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Cytochrome P-450 CYP1A2 / physiology*
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydroxyurea / analogs & derivatives*
  • Hydroxyurea / pharmacology
  • Lipoxygenase Inhibitors*
  • Male
  • Metabolic Clearance Rate
  • Theophylline / pharmacokinetics*

Substances

  • Enzyme Inhibitors
  • Lipoxygenase Inhibitors
  • Theophylline
  • Cytochrome P-450 CYP1A2
  • atreleuton
  • Hydroxyurea