Abstract

Background and objectives: The antimuscarinic drug trospium chloride is hydrophilic and therefore does not enter the CNS when used for the treatment of overactive bladder disturbances. However, the same property is the main reason for low and variable oral bioavailability. The present study was performed to assess the influence of intestinal site on absorption of the drug as the basis for the development of modified release preparations. Methods: In a change-over pilot study, 8 healthy male volunteers received single 20 mg doses of trospium chloride orally as a tablet (reference), as Eudragit-coated tablets dissolving at pH 6.0 (local administration into the small intestine), and rectally via a mini enema (corresponding to local administration into the large intestine). Plasma concentrations of trospium chloride were determined up to 36 hours after administration using GC/MS. Results: Extent and rate of trospium chloride absorption declined rapidly upon administration into more distal regions of the gastrointestinal tract. Cmax (median: 6.42 ng/ml) and AUC(0-tlast) (42.28 ng/ml × h) were highest and tmax (3.5 h) was shortest after administration of the reference tablet. AUC(0-tlast) reached 78% (90% CI 43 – 139%) after small intestine administration and 2% (90% CI 1 – 9%) following rectal administration, respectively, relative to the values for the oral tablet. Conclusion: Trospium chloride is absorbed primarily in the upper gastrointestinal tract. Development of modified release preparations must balance prolonged apparent absorption rates of the drug against a decrease in bioavailability.

Author Details

Authors

• S. Schröder¹
• A. Jetter¹
• M. Zaigler¹
• R. Weyhenmeyer²
• G. Krumbiegel²
• W. Wächter²
• U. Fuhr¹

Departments

• ¹ Department of Pharmacology, Clinical Pharmacology, University of Cologne, Cologne, and
• ² Madaus AG, Cologne, Germany

Address

Prof. Dr. U. Fuhr
Department of Pharmacology
University of Cologne, Clinical Pharmacology
Gleueler Straße 24
D-50931 Köln, Germany
Email: [email protected]

Log in for Subscribers

Citation