J Clin Pharmacol
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
0091270008321941v1
48/11/1339    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lahu, G.
Right arrow Articles by Zech, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lahu, G.
Right arrow Articles by Zech, K.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

DRUG INTERACTIONS

Effect of Single and Repeated Doses of Ketoconazole on the Pharmacokinetics of Roflumilast and Roflumilast N-Oxide

Gezim Lahu, MSc, Andreas Huennemeyer, MSc, MD, Oliver von Richter, PhD, Robert Hermann, MD, Rolf Herzog, Nigel McCracken, PhD and Karl Zech, PhD

From Nycomed GmbH (formerly ALTANA Pharma AG), Konstanz, Germany (Mr Lahu, Dr Huennemeyer, Mr Herzog, Dr McCracken, Dr von Richter, Dr Zech); University of Tuebingen, Institute for Toxicology, Pharmacy and Chemistry, Tuebingen, Germany (Mr Lahu); and Clinical Research Appliance, Radolfzell, Germany (Dr Hermann). Dr von Richter and Dr Hermann are fellows of the American College of Clinical Pharmacology.

Effects of single and multiple doses of oral ketoconazole on roflumilast and its active metabolite, roflumilast N-oxide, were investigated in healthy subjects. In study 1, subjects (n = 26) received oral roflumilast 500 µg once daily for 11 days and a concomitant 200-mg single dose of ketoconazole on day 11. In study 2, subjects (n = 16) received oral roflumilast 500 µg on days 1 and 11 and a repeated dose of ketoconazole 200 mg twice daily from days 8 to 20. Coadministration of single-dose ketoconazole with steady-state roflumilast increased the AUC of roflumilast by 34%; Cmax was unchanged. For roflumilast N-oxide, AUC and Cmax decreased by 12% and 20%, respectively. Repeated doses of ketoconazole increased the AUC and Cmax of roflumilast by 99% and 23%, respectively; for roflumilast N-oxide, AUC was unchanged, and Cmax decreased by 38%. No clinically relevant adverse events were observed. Coadministration of ketoconazole and roflumilast does not require dose adjustment of roflumilast.

Key Words: Drug-drug interactions • healthy subjects • ketoconazole • Phase 1 study • roflumilast

Address for reprints: Gezim Lahu, MSc, Nycomed GmbH, Department of Pharmacometrics and Pharmacokinetics, Byk-Gulden-Str. 2, 78467 Konstanz, Germany; e-mail: gezim.lahu{at}nycomed.com.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the American College of Clinical Pharmacology