Document Detail

Effect of repeated dose of erythromycin on the pharmacokinetics of roflumilast and roflumilast N-oxide.
MedLine Citation:
PMID:  19356389     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To investigate the effects of steady state erythromycin on the pharmacokinetics of roflumilast and its pharmacodynamically active metabolite roflumilast N-oxide in healthy subjects. Both roflumilast and roflumilast N-oxide have similar intrinsic PDE4 inhibitory activity; the total PDE4 inhibition (tPDE4i) in humans is likely due to the combined effect of roflumilast and roflumilast N-oxide. METHODS: Subjects (n = 16) received single oral roflumilast 500 microg once daily (Days 1 and 15), and repeated oral erythromycin 500 mg three times daily (Days 9 - 21). Percent ratios of Test/Reference (Reference: roflumilast alone; Test: roflumilast and steady-state erythromycin) were calculated for the geometric means and their 90% confidence intervals for systemic exposure (AUC), maximum concentration (Cmax) (roflumilast and roflumilast N-oxide), and apparent clearance of roflumilast. RESULTS: After co-administration of erythromycin and roflumilast, the mean AUC and Cmax of roflumilast increased by 70% and 40%, respectively. The mean apparent clearance of roflumilast decreased from 8.2 l/h (Reference) to 4.8 l/h (Test). Steady-state erythromycin did not alter the mean AUC of roflumilast N-oxide, however, the mean Cmax decreased by 34%. The AUCroflumilast N-oxide/AUCroflumilast ratio decreased from 10.6 (Reference) to 6.4 (Test). Co-administration of erythromycin and roflumilast did not influence the integrated total exposure to roflumilast and roflumilast N-oxide, i.e. mean tPDE4i. No clinically relevant adverse events were observed during the study. CONCLUSIONS: Co-administration of erythromycin (a moderate CYP3A4 inhibitor) and roflumilast does not require dose adjustment of roflumilast.
G Lahu; A Huennemeyer; R Herzog; N McCracken; R Hermann; M Elmlinger; K Zech
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of clinical pharmacology and therapeutics     Volume:  47     ISSN:  0946-1965     ISO Abbreviation:  Int J Clin Pharmacol Ther     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-09     Completed Date:  2009-06-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423309     Medline TA:  Int J Clin Pharmacol Ther     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  236-45     Citation Subset:  IM    
Nycomed GmbH (formerly ALTANA Pharma AG), Konstanz, Germany.
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MeSH Terms
Administration, Oral
Aminopyridines / adverse effects,  pharmacokinetics*
Anti-Bacterial Agents / administration & dosage,  adverse effects,  pharmacology
Area Under Curve
Benzamides / adverse effects,  pharmacokinetics*
Cross-Over Studies
Cyclic Nucleotide Phosphodiesterases, Type 4 / antagonists & inhibitors
Cyclopropanes / adverse effects,  pharmacokinetics
Cytochrome P-450 CYP3A / antagonists & inhibitors
Drug Interactions
Enzyme Inhibitors / administration & dosage,  adverse effects,  pharmacology
Erythromycin / administration & dosage,  adverse effects,  pharmacology*
Middle Aged
Phosphodiesterase Inhibitors / adverse effects,  pharmacokinetics*
Young Adult
Reg. No./Substance:
0/Aminopyridines; 0/Anti-Bacterial Agents; 0/Benzamides; 0/Cyclopropanes; 0/Enzyme Inhibitors; 0/Phosphodiesterase Inhibitors; 0/roflumilast; 0/roflumilast N-oxide; 114-07-8/Erythromycin; EC protein, human; EC P-450 CYP3A; EC Nucleotide Phosphodiesterases, Type 4

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