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Dose‐Proportional Intraindividual Single‐ and Repeated‐Dose Pharmacokinetics of Roflumilast, an Oral, Once‐Daily Phosphodiesterase 4 Inhibitor
Author(s) -
Bethke Thomas D.,
Böhmer Gabriele M.,
Hermann Robert,
Hauns Bernhard,
Fux Richard,
Mörike Klaus,
David Michael,
Knoerzer Dietrich,
Wurst Wilhelm,
Gleiter Christoph H.
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006294529
Subject(s) - roflumilast , pharmacokinetics , crossover study , medicine , dosing , pharmacology , confidence interval , oral administration , anesthesia , placebo , pulmonary disease , alternative medicine , pathology
The dose‐proportional, intraindividual, single‐ and repeated‐dose pharmacokinetics of roflumilast, an oral, once‐daily phosphodiesterase 4 inhibitor under investigation for chronic obstructive pulmonary disease and asthma, was investigated in healthy subjects. In an open, randomized, 2‐period, 2‐sequence crossover study, 15 subjects received immediate‐release tablets of roflumilast 250 or 500 μg as single (day 1) and as repeated, once‐daily doses for 8 days (days 5–12). Dose‐adjusted point estimates and 90% confidence intervals of test (500 μg)/reference (250 μg) ratios for AUC and C max of roflumilast and its pharmacologically active N‐oxide metabolite after single and repeated dosing were all within the standard equivalence acceptance range (0.80, 1.25) indicating dose proportionality. The pharmacokinetic properties of both roflumilast dosage forms provide clinically relevant evidence of predictable, intraindividual total (AUC) and maximum (C max ) exposure of roflumilast and roflumilast N‐oxide. Repeated oral dosing with roflumilast 250 and 500 μg once daily was well tolerated.