Pharmacodynamics of anticholinergic agents measured by ambulatory urodynamic monitoring: A study of methodology

The aim of the study was to establish a methodology whereby ambulatory urod ynamic monitoring (AUM) may be used in the assessment of the effects of dar ifenacin on urodynamic measures of detrusor function and symptoms associate d with detrusor instability. Six patients (one man and five women) with det rusor instability (DI) on conventional urodynamic monitoring were recruited into this placebo-controlled crossover study. The study was divided into t wo periods of 7 days of treatment with either darifenacin 5 mg t.d.s. or pl acebo with the patient crossing over to the alternative treatment after a w ashout period of 7 days. On the 7th day of each treatment, AUM was carried out. Parameters used to quantify detrusor activity on AUM were the number, amplitude, and duration of detrusor contractions and the total area under t he detrusor pressure/time curve. "Events" recorded were urge, leakage episo des, voids, and pain. Six comparable hours of AUM for each treatment period could be analyzed in four patients and 4 hr in one. In three of the five p atients, reduction in activity on AUM while on darifenacin was apparent. Sy mptom data closely matched the changes in detrusor activity measured on AUM . This is the first study reporting the use of AUM in the development of a dr ug with an effect on detrusor activity. AUM has clear advantages over conve ntional cystometry, which can only measure surrogate urodynamic parameters at a single time point. The optimal duration of monitoring in this context appears to be 6 hr with prolongation of monitoring time beyond this being u nlikely to yield additional useful information. Correlation between symptom s and findings on AUM is good with changes in parameters recorded on AUM re lating closely to the improvement in symptoms. (C) 1999 Wiley-Liss, Inc.