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:
0091270008315314v1
48/5/570    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
Google Scholar
Right arrow Articles by May, K.
Right arrow Articles by Siegmund, W.
PubMed
Right arrow PubMed Citation
Right arrow Articles by May, K.
Right arrow Articles by Siegmund, W.

PHARMACOKINETICS AND PHARMACODYNAMICS

Disposition and Antimuscarinic Effects of the Urinary Bladder Spasmolytics Propiverine: Influence of Dosage Forms and Circadian-Time Rhythms

Karen May, PhD, Kristin Westphal, MD, Thomas Giessmann, MD, Danilo Wegner, BSc, Ulrike Adam, PhD, Markus M. Lerch, MD, Reinhard Oertel, PhD, Rolf W. Warzok, MD, Werner Weitschies, PhD, Manfred Braeter, PhD and Werner Siegmund, MD

From the Department of Clinical Pharmacology (Dr May, Dr Giessmann, Mr Wegner, Dr Siegmund), Department of Anesthesiology and Intensive Care (Dr Westphal), Department of Biopharmacy and Pharmaceutical Technology (Dr Adam, Dr Weitschies), Department of Internal Medicine A (Dr Lerch), and Department of Pathology (Dr Warzok), University of Greifswald, Greifswald, Germany, and the Department of Clinical Pharmacology, University of Technology (Dr Oertel), and Apogepha Arzneimittel GmbH (Dr Braeter), Dresden, Germany. Manfred Braeter is an employee of APOGEPHA.

Propiverine extended release is expected to be better tolerated compared to immediate release tablets because of slower drug release and reduced formation of active metabolites in the colon. CYP3A4 and ABCC2, the major variables in pharmacokinetics of propiverine, are less expressed in the colon. Therefore, disposition and pharmacodynamics of propiverine were measured in a double-blind, double-dummy, crossover study with administration of 15 mg immediate release 3 times daily for 7 days compared to 45 mg extended release once daily for 7 days in 24 healthy subjects. Twelve subjects also received 15 mg propiverine intravenously. Serum and urine propiverine levels were measured repeatedly following oral administration on day 7 for up to 72 hours and correlated to duodenal expression of CYP3A4, ABCB1, and ABCC2. Propiverine immediate release 3 times daily was not different to extended release once daily in areas under the serum concentration-time curve (0-24 hours) and peak-trough fluctuation. The areas under the serum concentration-time curve of propiverine immediate release was circadian-time-dependent, with the lowest values during the night. Disposition of intravenous propiverine and propiverine immediate release administered in the night was influenced by intestinal expression of ABCC2. We concluded that oral absorption of propiverine is site-dependent and influenced by dosage form and circadian-time-dependent elimination processes.

Key Words: Propiverine • extended release • circadian rhythm • ABCC2

Address for correspondence: Prof. Werner Siegmund, Department of Clinical Pharmacology, Ernst Moritz Arndt University, Friedrich-Loeffler-Str. 23d, D-17487 Greifswald, Germany; e-mail: siegmuw{at}uni-greifswald.de.






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