Disease Information

General Information of the Disease (ID: DIS00135)

• Name: Overactive bladder
• ICD: ICD-11: GC50

Type(s) of Resistant Mechanism of This Disease

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Trospium chloride

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [1]

• Sensitive Disease: Overactive bladder [ICD-11: GC50.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Trospium chloride
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Mdr1a/1b double knockout mice xenograft model; Mus musculus
• Experiment for Drug Resistance: [3H]trospium chloride tissue distribution assay
• Mechanism Description: 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.

References

• Ref 1: The role of p-glycoprotein in limiting brain penetration of the peripherally acting anticholinergic overactive bladder drug trospium chloride. Drug Metab Dispos. 2009 Jul;37(7):1371-4. doi: 10.1124/dmd.109.027144. Epub 2009 Apr 23.