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 urodynamic monitoring (AUM) may be used in the assessment of the effects of darifenacin on urodynamic measures of detrusor function and symptoms associated with detrusor instability. Six patients (one man and five women) with detrusor instability (DI) on conventional urodynamic monitoring were recruited into this placebo-controlled crossover study. The study was divided into two periods of 7 days of treatment with either darifenacin 5 mg t.d.s. or placebo with the patient crossing over to the alternative treatment after a washout 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 the detrusor pressure/time curve. "Events" recorded were urge, leakage episodes, 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 patients, reduction in activity on AUM while on darifenacin was apparent. Symptom 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 drug with an effect on detrusor activity. AUM has clear advantages over conventional 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 unlikely to yield additional useful information. Correlation between symptoms and findings on AUM is good with changes in parameters recorded on AUM relating closely to the improvement in symptoms.
Rosario
D J
DJ
Department of Urology, Royal Hallamshire Hospital, Sheffield, United Kingdom. d.j.rosario@shef.ac.uk
Smith
D J
DJ
Radley
S C
SC
Chapple
C R
CR
D001572:Benzofurans / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D018670:Monitoring, Ambulatory / Q000379:methods*; D010342:Patient Acceptance of Health Care; D011446:Prospective Studies; D011759:Pyrrolidines / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D014555:Urination Disorders / Q000188:drug therapy* / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects
D001572:Benzofurans; D018680:Cholinergic Antagonists; D011759:Pyrrolidines; C101207:darifenacin