| Title | The role of P-glycoprotein in limiting brain penetration of the peripherally acting anticholinergic OAB drug trospium chloride. | | Author(s) | Geyer J, Gavrilova O, Petzinger E | | Institution | Justus Liebig University of Giessen. | | Source | Drug Metab Dispos 2009 Apr 23. | | 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 (OAB). P-gp deficient mdr1a,b(-/-) knockout mice were given either 1mg/kg trospium chloride orally or 1mg/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 to 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 CNS 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 to 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19389858 |
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