PURPOSE: To investigate the pharmacokinetics of intravesical oxybutynin and discuss the clinical implications of the results.
MATERIAL AND METHODS: Open-label, randomized, three period change-over clinical study including 20 healthy adult subjects. In period 1 and 2, subjects received single doses of either 10 mg oxybutynin-HCl solution intravesically or a 5 mg tablet orally. Period 3 comprised repeated intravesical applications (7 doses) of 10 mg oxybutynin-HCl. Enantioselective concentrations of oxybutynin and N-desethyloxybutynin (NDO) were quantified by LC-MS/MS. Pharmacokinetic parameters were calculated by non-compartmental methods, analyzed by descriptive statistics and compared using the average bioequivalence approach.
RESULTS: Systemic exposure to racemic oxybutynin following intravesical administration was significantly higher, yielding 294% (90%-CI: 211-408%) of that after oral intake of immediate-release preparations, as measured by dose-normalized AUC. By contrast, systemic exposure to racemic NDO reached only 21% (90%-CI: 15%-29%). The AUC-ratio of NDO/oxybutynin was 14-fold reduced for intravesical administration. Following intravesical multi-dose administration, cumulation of oxybutynin (1.3-fold) and NDO (1.6-fold) was weak, absorption was prolonged and apparent elimination half-lives were longer. The study medication was well tolerated, with a third of participants reporting anticholinergic adverse effects.
CONCLUSION: The present study provides evidence of a significantly higher bioavailability of intravesical versus oral oxybutynin administration by circumvention of the intestinal first-pass metabolism. Given the high efficacy and reduced rate of adverse effects, intravesical oxybutynin should be considered in patients with NLUTD who do not tolerate oral administration or in whom oral preparations fail to improve detrusor overactivity.
Written by:
Krause P, Fuhr U, Schnitker J, Albrecht U, Stein R, Rubenwolf P. Are you the author?
Itecra GmbH, Köln, Germany.
Reference: J Urol. 2013 May 10. pii: S0022-5347(13)04346-2.
doi: 10.1016/j.juro.2013.05.011
PubMed Abstract
PMID: 23669567
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