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Investigating detrusor muscle concentrations of oxybutynin after intravesical delivery in an Ex Vivo porcine model

Williams, Nicholas, Lee, Kay M., Allender, Christopher John, Bowen, Jenna L., Gumbleton, Mark, Harrah, Tim, Raja, Aditya and Joshi, Hrishi B. 2015. Investigating detrusor muscle concentrations of oxybutynin after intravesical delivery in an Ex Vivo porcine model. Journal of Pharmaceutical Sciences 104 (7) , pp. 2233-2240. 10.1002/jps.24471

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Abstract

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

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Publisher: WileyBlackwell
ISSN: 0022-3549
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 13 April 2015
Last Modified: 29 May 2018 09:12
URI: http://orca.cf.ac.uk/id/eprint/73826

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