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Investigation of a Potential Food Effect on the Pharmacokinetics of Roflumilast, an Oral, Once-Daily Phosphodiesterase 4 Inhibitor, in Healthy Subjects

From ALTANA Pharma AG, Konstanz, Germany. Supported by ALTANA Pharma AG, Konstanz, Germany.

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 µg (2 x 250 µg) 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 AUC_0-last, AUC_0-, and C_max of both compounds. After the meal, roflumilast C_max (PE, 0.59; 90% CI, 0.49-0.70) was modestly reduced; N-oxide C_max (PE, 0.95; 90% CI, 0.90-1.01) was unchanged. Roflumilast t_max was delayed in fed state (2.0 ± 0.4 hours) versus fasted state (1.0 ± 0.2 hours); N-oxide t_max was unaltered. No significant food effect on roflumilast AUC_0-last (PE, 1.04; 90% CI, 0.90-1.21), AUC_0- (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.

Key Words: Food effect • pharmacokinetics • phase I • phosphodiesterase 4 • roflumilast

Address for reprints: Dr. Bernhard Hauns, MD, Department of Clinical Pharmacology, ALTANA Pharma AG, Byk-Gulden-Str. 2, D-78467 Konstanz, Germany; e-mail: bernhard.hauns{at}altanapharma.com.

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