Pharmacokinetics of intravesical versus oral oxybutynin in healthy adults: results of an open label, randomized, prospective clinical study.

PURPOSE: We investigated the pharmacokinetics of intravesical oxybutynin and discuss the clinical implications of the results.

MATERIALS AND METHODS: We performed an open label, randomized, 3-period crossover clinical study in 20 healthy adults. In periods 1 and 2 subjects received a single dose of 10 mg oxybutynin HCl solution intravesically or a 5 mg tablet orally. Period 3 comprised repeat intravesical applications (7 doses) of 10 mg oxybutynin HCl. Enantioselective concentrations of oxybutynin and N-desethyloxybutynin were quantified by liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods, analyzed by descriptive statistics and compared using the average bioequivalence approach.

RESULTS: Systemic exposure to racemic oxybutynin after intravesical administration was significantly greater, yielding 294% (90% CI 211-408) of that after oral intake of immediate release preparations, as measured by the dose normalized area under the plasma concentration time curve. In contrast, systemic exposure to racemic N-desethyloxybutynin reached only 21% (90% CI 15-29). The area under the plasma concentration time curve ratio of N-desethyloxybutynin to oxybutynin was 14-fold decreased for intravesical administration. After intravesical multidose administration, the cumulation of oxybutynin (1.3-fold) and N-desethyloxybutynin (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.

CONCLUSIONS: Our study provides evidence of significantly higher bioavailability of intravesical vs oral administration of oxybutynin due to circumvention of the intestinal first pass metabolism. Given the high efficacy and decreased rate of adverse effects, intravesical oxybutynin should be considered in patients with neurogenic lower urinary tract dysfunction who do not tolerate oral administration or in whom oral preparations fail to improve detrusor overactivity.