Document Detail

Investigation of a potential food effect on the pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, in healthy subjects.
MedLine Citation:
PMID:  16988203     Owner:  NLM     Status:  MEDLINE    
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 microg (2 x 250 microg) 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-infinity), 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-infinity) (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.
Bernhard Hauns; Robert Hermann; Andreas Hünnemeyer; Rolf Herzog; Dieter Hauschke; Karl Zech; Thomas D Bethke
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  46     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-21     Completed Date:  2007-03-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1146-53     Citation Subset:  IM    
Department of Clinical Pharmacology, ALTANA Pharma AG, Byk-Gulden-Str. 2, D-78467 Konstanz, Germany.
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MeSH Terms
3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
Administration, Oral
Aminopyridines / administration & dosage,  blood,  metabolism,  pharmacokinetics*
Area Under Curve
Benzamides / administration & dosage,  blood,  metabolism,  pharmacokinetics*
Cross-Over Studies
Cyclic Nucleotide Phosphodiesterases, Type 4
Cyclopropanes / administration & dosage,  blood,  metabolism,  pharmacokinetics
Dietary Fats / administration & dosage*,  adverse effects,  pharmacokinetics
Food-Drug Interactions*
Headache / diagnosis,  epidemiology
Phosphodiesterase Inhibitors / administration & dosage,  adverse effects,  pharmacokinetics*
Reg. No./Substance:
0/Aminopyridines; 0/Benzamides; 0/Cyclopropanes; 0/Dietary Fats; 0/Phosphodiesterase Inhibitors; 0/roflumilast; 0/roflumilast N-oxide; EC',5'-Cyclic-AMP Phosphodiesterases; EC Nucleotide Phosphodiesterases, Type 4

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