The major metabolic pathway is hypothesized as ester hydrolysis with subsequent conjugation of benzylic acid to form azoniaspironortropanol with glucuronic acid. Cytochrome P450 is not expected to contribute significantly to the elimination of trospium. Data taken from in vitro human liver microsomes investigating the inhibitory effect of trospium on seven cytochrome P450 isoenzyme substrates (CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4) suggest a lack of inhibition at clinically relevant concentrations.The plasma half-life for trospium chloride following oral administration is approximately 20 hours. After oral administration of an immediate-release formulation of 14C-trospium chloride, the majority of the dose (85.2%) was recovered in feces and a smaller amount (5.8% of the dose) was recovered in urine; 60% of the radioactivity excreted in urine was unchanged trospium. The mean renal clearance for trospium (29 L/hour) is 4-fold higher than average glomerular filtration rate, indicating that active tubular secretion is a major route of elimination for trospium. There may be competition for elimination with other compounds that are also renally eliminated. Chemical properties
Anticholinergic drugs used to treat overactive bladder were all amines as of 2003. Quaternary ammonium cations in general are more hydrophilic than other amines and dont cross membranes well, so they tend to be poorly absorbed from the digestive system, and to not cross the blood-brain barrier. Oxybutynin, tolterodine, darifenacin, and solifenacin are tertiary amines while trospium chloride and propantheline are quaternary amines.
Indevus had developed intellectual property around the extended release formulation which it licensed to Madaus for most of the world.In 2012 the FDS approved the first generic version of the extended release formulation, granting approval to the ANDA that Watson Pharmaceuticals had filed in 2009. Annual sales in the US at that time were $67M. European patents had expired in 2009.As of 2016, the drug is available worldwide under many brand names and formulations, including oral, extended release, suppositories, and injections. Society and culture
Marketing rights to the drug became subject to parallel import litigation in Europe in the case of Speciality European Pharma Ltd v Doncaster Pharmaceuticals Group Ltd / Madaus GmbH (Case No. A3/2014/0205) which was resolved in March 2015. Madaus had exclusively licensed the right to use the Regurin trademark to Speciality European Pharma Ltd. In 2009, when European patents expired on the drug, Doncaster Pharmaceuticals Group, a well known parallel importer, which had been selling the drug in the UK under another label, Ceris, which was used in France, began to put stickers on their packaging with the Regurin name. Speciality and Madaus sued and initially won based on the argument that 90% of prescriptions were already generic, but Doncaster appealed and won the appeal based on the argument that it could not charge a premium with a generic label. The case has broad implications for trade in the EU.