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Oxybutynin is used to treat patients with urinary urgency, frequency, and urge incontinence. In this 2-way, multipledose, crossover study, the pharmacokinetics and pharmacodynamics of once-daily controlled-release oxybutynin were compared with immediate-release oxybutynin. Eighteen healthy male volunteers received one 15-mg controlled-release oxybutynin tablet once daily for 5 days or one 5-mg immediate-release oxybutynin tablet every 8 hours for 5 days. The washout period between treatments was ≥7 days. The mean steady-state AUC for oxybutynin following controlled-release oxybutynin treatment was higher (73.0 ng·h/mL) than following immediate-release oxybutynin treatment (53.6 ng·h/mL) (P = .0001). The mean Cmax was lower for controlled-release oxybutynin (5.7 ng/mL) than for immediate-release oxybutynin (7.5 ng/mL) (P = .0051), with a smaller fluctuation in oxybutynin plasma concentration for controlled-release oxybutynin (135.6%) than for immediate-release oxybutynin (319.3%) (P = .0001). Mean stimulated saliva output was greater for controlled-release oxybutynin, and mean dry mouth severity was less than immediate-release oxybutynin.