Tolterodine is a potent
antimuscarinic agent specifically developed for the treatment of
urinary urge incontinence and other symptoms related to the
overactive bladder. In order to assess the optimum dosage for use in future clinical studies, a double-blind, randomized, placebo-controlled, parallel-group, multicenter study was performed in 90 patients with detrusor
hyperreflexia and symptoms of urinary urgency, frequency, and/or
urge incontinence. Urodynamic variables, micturition diary variables, and subjective urinary symptoms were measured before and after 2 weeks' treatment with either placebo or
tolterodine 0.5, 1, 2, or 4 mg twice daily (bd). Serum
drug concentrations, electrocardiogram recordings, blood pressure, and incidence of adverse events were also assessed. Linear regression analysis showed a significant dose-response relationship for several clinically relevant urodynamic variables, while there was a trend towards an improvement in micturition diary variables and subjective assessment of symptoms with increasing dosages of
tolterodine. There were no safety or tolerability concerns regarding any of the dosages of
tolterodine investigated, although 2 patients treated with a dosage of 4 mg bd experienced
urinary retention that necessitated dosage reduction. The results of this study suggest that
tolterodine is well-tolerated and exerts a dose-dependent effect on bladder function in patients with detrusor
hyperreflexia. The optimum dosage of
tolterodine for use in future studies is 1-2 mg bd.