Intravesical
oxybutynin is highly effective in the treatment of
overactive bladder. Traditionally the mechanism of action was explained by antagonism of
muscarinic receptors located in the detrusor, however evidence now suggests
antimuscarinics may elicit their effect by modifying afferent pathways in the mucosal region. This study aimed to investigate the bladder wall distribution of
oxybutynin in an ex vivo setting providing tissue - layer specific concentrations of
drug achieved after intravesical delivery. Whole ex vivo porcine bladders were intravesically instilled with 0.167 mg mL(-1)
oxybutynin solution. After 60 min, tissue samples were excised, serially sectioned parallel to the urothelial surface and extracted
drug quantified.
Drug distribution into the urothelium, lamina propria and detrusor was determined.
Oxybutynin permeated into the bladder wall at a higher rate than other drugs previously investigated (apparent transurothelial Kp = 1.36 × 10(-5) cm s(-1) ). After 60 min
intravesical instillation, concentrations achieved in the urothelium (298.69 μg g(-1) ) and lamina propria (43.65 μg g(-1) ) but not the detrusor (0.93 μg g(-1) ) were greater than reported IC50 values for
oxybutynin. This work adds to the increasing body of evidence suggesting
antimuscarinics elicit their effects via mechanisms other than direct inhibition of detrusor contraction.