Lack of cytochrome P450 1A2 interaction effect of ABT-761 on the pharmacokinetics of theophylline.
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.
Wong
S L
SL
Department of Pharmacokinetics and Biopharmaceutics, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Cavanaugh
J H
JH
Qian
J
J
Hansen
R
R
Awni
W M
WM
D000328:Adult; D019388:Cytochrome P-450 CYP1A2 / Q000502:physiology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008297:Male; D008657:Metabolic Clearance Rate; D013806:Theophylline / Q000493:pharmacokinetics*
D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D013806:Theophylline; D019388:Cytochrome P-450 CYP1A2; C096921:atreleuton; D006918:Hydroxyurea