Pharmacokinetic characteristics of roflumilast administered in gradually increasing doses of 500μg to 1000μg are dose-linear in healthy subjects A. Manegold, B. Hauns, M. David, K. Zech, T. D. Bethke, W. Wurst (Konstanz, Germany)
Source: Annual Congress 2002 - Asthma and COPD: pharmacology
Session: Asthma and COPD: pharmacology Session type: Thematic Poster Session Number: 742
Disease area: Airway diseasesAbstract Roflumilast (ROF) is a novel, orally active, selective PDE4 inhibitor, administered once-daily for treatment of COPD and bronchial asthma. We investigated the pharmacokinetic characteristics AUC and Cmax in a double blind, parallel-group comparison with 18 healthy subjects (17 m, 1 f; age 21-26 y). The subjects received a daily dose of 500μg (days 1-7), 750μg (days 8-14) and 1000μg ROF (days 15-21). Plasma concentrations of ROF were measured by HPLC. No relevant changes in vital signs, ECG, laboratory parameters, and in frequency of adverse events were observed with increasing doses of ROF. Pharmacokinetic characteristics of ROF and its active metabolite ROF-N-oxide on day 7 (500μg ROF), day 14 (750μg ROF) and day 21 (1000μg ROF) are shown in the table below.
Geometric means (68%-range)
500μg ROF
750μg ROF
1000μg RO
ROF
AUC [μg*h/l]
32.6 (24.0 - 44.4)
50.8 (36.9 - 70.0)
65.9 (49.5 - 87.8)
Cmax [μg/l]
4.7 (3.7 - 6.1)
8.2 (6.042 - 11.0)
11.1 (8.3 - 15.0)
t1/2 [h]
14.3 (9.0 - 22.8)
13.7 (8.7 - 21.7)
14.7 (10.4 - 20.7)
ROF-N-oxide
AUC [μg*h/l]
347.2 (284.7 - 423.3)
587.3 (462.3 - 746.2)
799.9 (638.5 - 1002.1)
Cmax [μg/l]
20.7 (17.2 - 24.8)
33.7 (27.3 - 41.7)
50.6 (43.7 - 58.5)
t1/2 [h]
--
--
19.6 (15.1 - 25.6)
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A. Manegold, B. Hauns, M. David, K. Zech, T. D. Bethke, W. Wurst (Konstanz, Germany). Pharmacokinetic characteristics of roflumilast administered in gradually increasing doses of 500μg to 1000μg are dose-linear in healthy subjects. Eur Respir J 2002; 20: Suppl. 38, 742
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