Investigation of a Potential Food Effect on the Pharmacokinetics of Roflumilast, an Oral, Once-Daily Phosphodiesterase 4 Inhibitor, in Healthy Subjects.
Hauns, Bernhard MD; Hermann, Robert MD; Hunnemeyer, Andreas MD; Herzog, Rolf; Hauschke, Dieter PhD; Zech, Karl PhD; Bethke, Thomas D. MD
Journal of Clinical Pharmacology.
46(10):1146-1153, October 2006.
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This open, randomized, single-dose crossover study investigated effects of a high-fat meal on the pharmacokinetics of roflumilast and its major active N-oxide metabolite. Twelve healthy subjects received oral roflumilast 500 [mu]g (2 x 250 [mu]g) after overnight fasting and after breakfast. Blood was sampled up to 54 hours for pharmacokinetic profiling of roflumilast and N-oxide. Geometric mean ratios (fed/fasted) for point estimates (PE) and 90% confidence intervals (CI) were calculated for AUC0-last, AUC0-[infinity], and Cmax of both compounds. After the meal, roflumilast Cmax (PE, 0.59; 90% CI, 0.49-0.70) was modestly reduced; N-oxide Cmax (PE, 0.95; 90% CI, 0.90-1.01) was unchanged. Roflumilast tmax was delayed in fed state (2.0 /- 0.4 hours) versus fasted state (1.0 /- 0.2 hours); N-oxide tmax was unaltered. No significant food effect on roflumilast AUC0-last (PE, 1.04; 90% CI, 0.90-1.21), AUC0-[infinity] (PE, 1.12; 90% CI, 1.00-1.25), and respective N-oxide AUCs (PE, 0.91; 90% CI, 0.79-1.04; PE, 0.99; 90% CI, 0.92-1.06) occurred. Because roflumilast N-oxide is the major contributor to roflumilast's overall pharmacologic effects, these findings suggest that roflumilast can be taken with or without food.
(C)2006 SAGE Publications