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

Abstract

Roflumilast (ROF) is a novel, orally active selective PDE4 inhibitor, which is administered on a once-daily basis for treatment of COPD and bronchial asthma. The aim of this study was to evaluate the influence of age on pharmacokinetic characteristics of ROF and ROF-N-oxide. In an open, one-period study, 12 healthy subjects (10 m, 2 f, age 45-64 y) received one single oral dose of 500μg ROF. The pharmacokinetic characteristics AUC, Cmax and t1/2 were determined. Vital signs, ECG, laboratory parameters, and adverse events were assessed. No relevant changes in safety parameters were observed and no serious adverse events occured. A cross-study comparison with 12 healthy young subjects (10 m, 2 f, age 22-30 y) was performed. The AUCs of ROF and ROF-N-oxide increased in the middle aged as compared to the young subjects. Cmax of ROF also increased, however with respect to ROF-N-oxide, no significant change was observed. Point estimates (90%-CI) for the ratios of the test (middle aged: 45-64 y) and reference (young: 22-30 y) population medians were similar as shown in the table below.

	Point estimates (90%-CI)
	AUC	Cmax	t1/2
ROF	1.16 (0.94, 1.44)	1.41 (1.13, 1.76)	1.50 (1.11, 2.02)
ROF-N-oxide	1.26 (1.04, 1.53)	1.02 (0.87, 1.18)	1.50 (1.12, 2.00)

Thus, dose adjustment of ROF is not considered to be necessary in middle aged subjects. A single oral dose of 500μg ROF is safe and well tolerated.

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Citations should be made in the following way:
A. Manegold, A. Huennemayer, K. Zech, B. Hauns, M. David, T. D. Bethke, W. Wurst (Konstanz, Germany). Pharmacokinetics of roflumilast and its active metabolite roflumilast-N-oxide in middle aged and young subjects. Eur Respir J 2002; 20: Suppl. 38, 744

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