Journal article

Publication year: 2009

Pages: 1371-1374

Journal: Drug Metabolism and Disposition

Volume number: 37

Issue number: 7

ISSN: 0090-9556

eISSN: 1521-009X

DOI Link: https://doi.org/10.1124/dmd.109.027144

Publisher: American Society for Pharmacology and Experimental Therapeutics (ASPET)

Abstract: 
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.

Harvard Citation style: Geyer, J., Gavrilova, O. and Petzinger, E. (2009) The Role of P-Glycoprotein in Limiting Brain Penetration of the Peripherally Acting Anticholinergic Overactive Bladder Drug Trospium Chloride, Drug Metabolism and Disposition, 37(7), pp. 1371-1374. https://doi.org/10.1124/dmd.109.027144

APA Citation style: Geyer, J., Gavrilova, O., & Petzinger, E. (2009). The Role of P-Glycoprotein in Limiting Brain Penetration of the Peripherally Acting Anticholinergic Overactive Bladder Drug Trospium Chloride. Drug Metabolism and Disposition. 37(7), 1371-1374. https://doi.org/10.1124/dmd.109.027144