title: Pharmacokinetics of intravesical versus oral oxybutynin in healthy adults: results of an open label, randomized, prospective clinical study.
abstract: OBJECTIVE
  We investigated the pharmacokinetics of intravesical oxybutynin and discuss the clinical implications of the results.
  
  
  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.
authors.affiliation: Itecra GmbH, Köln, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Krause
authors.forename: Uwe
authors.initials: U
authors.lastname: Fuhr
authors.forename: Jörg
authors.initials: J
authors.lastname: Schnitker
authors.forename: Uwe
authors.initials: U
authors.lastname: Albrecht
authors.forename: Raimund
authors.initials: R
authors.lastname: Stein
authors.forename: Peter
authors.initials: P
authors.lastname: Rubenwolf
mesh_terms: D000283:Administration, Intravesical; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D006801:Humans; D008333:Mandelic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged; D011446:Prospective Studies; D064804:Urological Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D008333:Mandelic Acids; D064804:Urological Agents; C005419:oxybutynin
keywords: ADR; AE; AUC; AUC extrapolated to infinity; AUC(∞); C(max); N-desethyloxybutynin HCl; NDO; NLUTD; OXY; PK; R; R-enantiomer; S; S-enantiomer; adverse drug reaction; adverse effect/event; adverse effects; apparent terminal elimination half-life; area under plasma concentration time curve; desethyloxybutynin; neurogenic lower urinary tract dysfunction; oxybutynin; oxybutynin HCl; peak plasma concentration; pharmacokinetics; t(1/2); t(max); time to peak plasma concentration; urinary bladder