ABSTRACT
Introduction and Objectives: Multiple LUTS frequently co-occur, but little is known about the prevalence and patient impact of symptom combinations. A large, multi-country epidemiological study examined the prevalence and impact of LUTS in men and women over 40 in the US, UK, and Sweden.
Introduction and Objectives
The Refractory Urge Incontinence and Botulinum A Toxin Injection (RUBI) randomized clinical trial was designed to compare the effect of 200 U of intra-detrusor Botulinum A toxin (BoNT-A) versus placebo on improvement in urge incontinence symptoms in neurologically normal women with DOI refractory to at least two first-line treatments.
ABSTRACT
Introduction and Objectives: Agents that can easily penetrate the blood-brain barrier (i.e., those with high lipophilicity at physiologic pH) may potentiate central nervous system (CNS) effects. The ability of antimuscarinic agents currently available for the treatment of overactive bladder (OAB) to cross the blood-brain barrier and cause cognitive impairment is of concern, particularly in elderly patients. Fesoterodine (FESO) is a new antimuscarinic agent for the treatment of OAB that is rapidly and extensively hydrolyzed by nonspecific esterases to its only active moiety, 5-hydroxymethyl tolterodine (5-HMT), which is chemically identical to the major active metabolite of tolterodine (Tubaro, A., and C. DeNunzio. [2004]. EAU Update Series 2: 161-169). It has been previously reported that tolterodine, a tertiary amine, has low lipophilicity and low CNS penetration (brain/blood ratio: 0.1 to 0.3 for radioactivity) in mice (Nilvebrant L. Rev Contemp Pharmacother. 2000;11:13-27). A comparison of the chemical structure of tolterodine and 5-HMT suggests that the latter is even less lipophilic owing to hydroxylation. Based on OECD Test Guideline (Nasal, A., et al. [2003]. Curr Med Chem 10: 381-426), the octanol:water distribution coefficient (logD) at pH 7.4 is commonly used to indicate lipophilicity of substances at the pH of blood plasma. The objective of this study was to determine the lipophilicity of 5-HMT compared with antimuscarinic agents currently used for treatment of OAB.
Introduction and Objectives
OAB is common in older pts, as are comorbidities that can impact a pt’s risk for experiencing AEs.
Introduction and Objectives
We studied the role of muscarinic receptor subtype on urothelium and detrusor in rats with detrusor overactivity induced by bladder outlet obstruction (BOO).
