Format

Send to

Choose Destination
Int J Clin Pharmacol Ther. 2009 Apr;47(4):236-45.

Effect of repeated dose of erythromycin on the pharmacokinetics of roflumilast and roflumilast N-oxide.

Author information

1
Nycomed GmbH (formerly ALTANA Pharma AG), Konstanz, Germany. gezim.lahu@nycomed.com

Abstract

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.

PMID:
19356389
DOI:
10.5414/cpp47236
[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center