Flavoxate 250mg/5ml oral suspension

BackgroundPersistence with antimuscarinic therapy in overactive bladder (OAB) is poor, but may be different for mirabegron, a β3-adrenoceptor agonist with a different adverse event profile.ObjectiveTo compare persistence and adherence with mirabegron versus tolterodine extended release (ER) and other antimuscarinics in routine clinical practice over a 12-mo period.Design, setting, and participantsRetrospective, longitudinal, observational study of anonymised data from the UK Clinical Practice Research Datalink GOLD database. Eligibility: age ≥18 yr, ≥1 prescription for target OAB drug (between May 1, 2013 and June 29, 2014), and 12-mo continuous enrolment before and after the index prescription date.InterventionsMirabegron, darifenacin, fesoterodine, flavoxate, oxybutynin ER or immediate-release (IR), propiverine, solifenacin, tolterodine ER or IR, and trospium chloride.Outcome measurements and statistical analysisThe primary endpoint was persistence (time to discontinuation). Secondary endpoints included 12-mo persistence rates and adherence (assessed using medication possession ratio, MPR). Cox proportional-hazards regression models and logistic regression models adjusted for potential confounding factors were used to compare cohorts. Analyses were repeated after 1:1 matching.Results and limitationsThe study population included 21996 eligible patients. In the unmatched analysis, the median time-to-discontinuation was significantly longer for mirabegron (169 d, interquartile range [IQR] 41-not reached) compared to tolterodine ER (56 d, IQR 28-254; adjusted hazard ratio [HR] 1.55, 95% confidence interval 1.41-1.71; pConclusionsPersistence and adherence were statistically significantly greater with mirabegron than with tolterodine ER and other antimuscarinics prescribed for OAB in the UK.Patient summaryThis study assessed persistence and adherence (or compliance) with medications prescribed for OAB in a large UK population. We found that patients prescribed mirabegron remained on treatment for longer and showed greater adherence than those prescribed traditional antimuscarinics.

Abstract licence: CC BY-NC-ND

Given that (hetero)aryl carboxylic acids are inexpensive materials available in a great variety from commercial and natural resources or synthesis, the strategies enabling their use as starting materials for preparing fine chemicals are highly sought after. Here we report a photoinduced Cu(II)-mediated protocol converting (hetero)aryl carboxylic acids into (hetero)aryl thianthrenium salts, high value-added building blocks that can undergo various subsequent transformations, creating an attractive two-step pathway for the divergent functionalization of these ubiquitous starting materials. The excellent compatibility of the method is shown by preparing a broad range of sterically and electronically varied (hetero)aryl thianthrenium salts, including derivatives of pharmaceuticals, such as ataluren, celecoxib, flavoxate, probenecid, repaglinide, and tamibarotene. The syntheses of 13 C-labeled probenecid and bioisosteres of ataluren as well as the unconventional modifications of celecoxib and flavoxate, illustrate the synthetic potential of the strategy. Mechanistic studies are in line with a reaction occurring through a photoinduced ligand-to-metal charge transfer (LMCT) of Cu(II)-arylcarboxylates, enabling radical decarboxylative carbometallation to form arylcopper(II) intermediates that in turn react with thianthrene to form the product. Noteworthy, the susceptibility of aryl thianthrenium salts to photodegradation is overcome by a Cu(I)-driven salvage loop, which continuously intercepts the transiently formed radicals and regenerates the products.

Abstract licence: CC BY