DMD Simcyp

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on April 23, 2009; DOI: 10.1124/dmd.109.027144

0090-9556/09/3707-1371-1374$20.00
DMD 37:1371-1374, 2009

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.109.027144v1
37/7/1371    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
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
Google Scholar
Right arrow Articles by Geyer, J.
Right arrow Articles by Petzinger, E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Geyer, J.
Right arrow Articles by Petzinger, E.
SHORT COMMUNICATION

The Role of P-Glycoprotein in Limiting Brain Penetration of the Peripherally Acting Anticholinergic Overactive Bladder Drug Trospium Chloride

Joachim Geyer, Olga Gavrilova, and Ernst Petzinger

Institute of Pharmacology and Toxicology, Justus Liebig University of Giessen, Giessen, Germany

The aim of the present study was to characterize the role of the drug-efflux transporter P-glycoprotein (P-gp) for the disposition of trospium chloride, a widely used anticholinergic drug for the treatment of overactive bladder. P-gp-deficient mdr1a,b(–/–) knockout mice were given either 1 mg/kg trospium chloride orally or 1 mg/kg intravenously to analyze brain penetration, intestinal secretion, and hepatobiliary excretion of the drug. The concentrations of trospium chloride in the brain were up to 7 times higher in the mdr1a,b(–/–) knockout mice compared with wild-type mice (p < 0.05), making P-gp a limiting factor for the blood-brain barrier penetration of this drug. Moreover, the residence time of the drug in the central nervous system was significantly prolonged in mdr1a,b(–/–) knockout mice. Apart from the blood-brain barrier, P-gp also had significant effects on the overall pharmacokinetics of trospium chloride. In the mdr1a,b(–/–) knockout mice, hepatobiliary excretion and intestinal secretion were significantly reduced compared with the wild-type mice. Our study indicates that the multidrug resistance transporter P-gp is a major determinant for the distribution of trospium chloride in the body and highly restricts its entry into the brain.

Address correspondence to: Prof. Dr. Joachim Geyer, Institute of Pharmacology and Toxicology, Justus Liebig University of Giessen, Frankfurter Str. 107, 35392 Giessen, Germany. E-mail: Joachim.M.Geyer{at}vetmed.uni-giessen.de






Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2009 by the American Society for Pharmacology and Experimental Therapeutics.