Dose-Ranging Study Of Tolterodine In
Van Kerrebroeck PE, Amarenco G, Thuroff JW, Madersbacher HG, Lock MT, Messelink EJ, Soler JM
Neurourol Urodyn 1998;17(5):499-512
Univ Hospital Maastricht, The Netherlands
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.
Efficacy & Safety Of Tolterodine In Detrusor Instability
Rentzhog L, Stanton SL, Cardozo L, Nelson E, Fall M, Abrams P
Br J Urol 1998 Jan;81(1):42-8
Sundsvall Hospital, Sweden
To investigate the efficacy and safety of Tolterodine, a new AntiMuscarinic agent, and define the optimum dosage in patients with symptoms of Detrusor instability (Urgency, Increased Frequency of Micturition and/or Urge Incontinence).
Patients & Methods
A double-blind, placebo-controlled, multicenter study was carried out; after a 1-week run-in period to establish baseline values, 81 patients were randomized to receive placebo or Tolterodine 0.5, 1, 2 or 4 mg twice daily for 2 weeks.
Micturition (diary) variables, Urodynamics and subjective Urinary symptoms were assessed after 2 weeks' treatment.
A per-protocol analysis of efficacy in 64 patients showed dose-related improvements in recorded Micturition and Urodynamic variables, e.g. at a dosage of 2 mg twice daily.
The frequency of Micturition, episodes of Incontinence and pad use were reduced by 20%, 46% and 29%, respectively, while the volume at first contraction increased by 89 mL.
The 4 mg dosage was associated with a large increase in residual Urinary Volume and an increased incidence of Dry Mouth. The incidence of adverse events (mainly mild or moderate AntiMuscarinic effects) was comparable with placebo at Tolterodine dosages of < or = 2 mg.
No serious adverse events were observed and Tolterodine had no clinically significant impact on ElectroCardiographic or laboratory findings.
The results indicate that Tolterodine offers an effective treatment for the symptoms of Detrusor Instability. The optimum dosage appears to be 1-2 mg twice daily.