Source: Annual Congress 2002 - Asthma and COPD: pharmacology
Disease area: Airway diseases

Abstract

Roflumilast (ROF) is a novel, orally active, selective PDE4 inhibitor, administered once-daily for treatment of COPD and bronchial asthma. ROF-N-oxide is the major metabolite formed in vivo and mainly responsible for efficacy. We investigated the effect of food intake on pharmacokinetic characteristics of ROF and ROF-N-oxide in an open, randomized, 2-period cross-over study with 12 healthy subjects (10 m, 2 f; age 22-30 y) who received a single oral dose of 500μg ROF after intake of a fat-rich breakfast (reference) or in a state of fasting (test). Plasma concentrations of ROF and ROF-N-oxide were measured by HPLC. Vital signs, ECG, laboratory parameters and adverse events were assessed. No relevant changes in vital signs were observed and no serious adverse events occurred. Food intake led to a reduced Cmax of ROF. However, AUC values of ROF and ROF-N-oxide were similar with or without food. Point estimates (90%-CI) for the ratios of the test (fasting) and reference (non-fasting) population medians after a single oral dose of 500μg ROF are shown in the table below.

	Point estimates (90%-CI)
Parameter	ROF	ROF-N-oxide
AUC	1.12 (1.00, 1.25)	0.91 (0.79, 1.04)
Cmax	0.59 (0.49, 0.70)	0.95 (0.90, 1.01)

The data indicate that food intake has no relevant influence on the AUC of ROF and ROF-N-oxide, and hence on its therapeutic efficacy. ROF is safe and well tolerated, regardless whether taken under conditions of fasting or non-fasting.

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Citations should be made in the following way:
A. Drollmann, A. Huennemayer, M. Hartmann, B. Hauns, K. Zech, T. D. Bethke, W. Wurst (Konstanz, Germany). Pharmacokinetic characteristics of roflumilast and its active metabolite roflumilast-N-oxide are not affected by food intake. Eur Respir J 2002; 20: Suppl. 38, 747

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