Intravesical oxybutynin: Mode of action assessed by passive diffusion and electromotive administration with pharmacokinetics of oxybutynin and N-desethyl oxybutynin

Purpose: A proportion of patients with detrusor hyperreflexia who are unres ponsive to oral oxybutynin often benefit from intravesical oxybutynin insti llation. To our knowledge the precise mode of action of this method is obsc ure. Materials and Methods: In 12 patients with detrusor hyperreflexia who were previously unresponsive to oral and intravesical passive diffusion of 5 mg. oxybutynin we administered 5 mg. oxybutynin orally as well as increased do ses of 15 mg. oxybutynin intravesically with passive diffusion and with 15 mA. associated electric current. Each administration mode per patient was a ssociated with an 8-hour urodynamic monitoring session during which oxybuty nin and N-desethyl oxybutynin plasma levels, and intravesical oxybutynin up take were measured. Results: A dose of 5 mg. oxybutynin orally induced no urodynamic improvemen t with an area under the plasma concentration time curve of combined N-dese thyl oxybutynin plus oxybutynin of 16,297 ng./8 hours and an area under the curve ratio of N-desethyl oxybutynin-to-oxybutynin of 11:1. Passive diffus ion oxybutynin resulted in 12 mg. oxybutynin intravesical uptake and signif icant improvement in 3 of 8 urodynamic measurements, although the area unde r the curve of combined N-desethyl oxybutynin plus oxybutynin was only 2,12 3 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was 1.1:1.0 . Electromotive administration of oxybutynin resulted in almost complete in travesical uptake of the 15 mg. dose, significant improvement in all 8 urod ynamic measurements and an increased oxybutynin level versus oral and passi ve diffusion, although the area under the curve of combined N-desethyl oxyb utynin plus oxybutynin was 4,574 ng./8 hours and the N-desethyl oxybutynin- to-oxybutynin ratio was inverted at 1.0:1.4. The oral dose of 5 mg. oxybuty nin caused anticholinergic side effects in 8 of the 12 patients. Neither in travesical passive diffusion nor electromotive administration caused side e ffects with an uptake of 12 and 15 mg., respectively. Conclusions: A large proportion of intravesical oxybutynin is sequestered, probably in the urothelium. Intravesical oxybutynin administration confers therapeutic benefits via localized direct action within the bladder wall.