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

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.

• Authors: S L Wong, J H Cavanaugh, J Qian, R Hansen, W M Awni
• Journal: American journal of therapeutics (Am J Ther) Vol. 5 Issue 5 Pg. 303-6 (Sep 1998) ISSN: 1075-2765 [Print] United States
• PMID: 10099073 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

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

Topics

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