Fesoterodine

Solid
Fesoterodine is a diarylmethane.|Fesoterodine is an antimuscarinic prodrug for the treatment of overactive bladder syndrome.|Fesoterodine is an anticholinergic and antispasmotic agent used to treat urinary incontinence and overactive bladder syndrome. Fesoterodine has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury.|Fesoterodine is a competitive muscarinic receptor antagonist with muscle relaxant and urinary antispasmodic properties. Fesoterodine is rapidly hydrolyzed in vivo into its active metabolite 5-hydroxy methyl tolterodine, which binds and inhibits muscarinic receptors on the bladder detrusor muscle, thereby preventing bladder contractions or spasms caused by acetylcholine. This results in the relaxation of bladder smooth muscle and greater bladder capacity, in addition to a reduction in involuntary muscle contractions and involuntary loss of urine. The active metabolite does not interact with alpha-adrenergic, serotonergic, histaminergic and excitatory amino acid receptors and is eliminated via renal excretion.
Fesoterodine, launched for the treatment of OAB, is an orally active pro-drug that is converted in vivo to its active metabolite 5-HMT through hydrolysis by non-specific esterases. 5-HMT is also an active metabolite of tolterodine (Detrol), which has been marketed for the treatment of OAB since 1998. 5-HMT is a potent muscarinic antagonist, with essentially equivalent affinity for M1, M2, M3, M4, and M5 receptors (Ki＝0.32, 0.63, 1.26, 2, and 0.63 nM, respectively). The binding of 5-HMT is stereoselective; the corresponding S-enantiomer has at least 100 times lower binding affinity for all five receptors. Fesoterodine is supplied as its fumarate salt in an extended release tablet form. The recommended starting dose is 4 mg once daily. On the basis of individual response and tolerability, the dose may be increased to 8 mg once daily. Following oral administration, fesoterodine is not detected in the peripheral blood, thereby indicating a rapid and complete bioconversion to 5-HMT. Bioavailability of 5-HMT is about 52%. After single- or multiple-dose oral administration of fesoterodine in doses from 4 to 28 mg, plasma concentrations of 5-HMT are proportional to the dose. Maximum plasma levels are reached after approximately 5 h. No accumulation occurs after multiple-dose administration. 5-HMT is further metabolized in the liver through oxidation of the hydroxymethyl group and oxidative cleavage of N-alkyl groups mediated by CYP2D6 and CYP3A4. 5-HMT and its metabolites are primarily eliminated through renal excretion.The most common adverse events associated with fesoterodine include dry mouth, constipation, and dyspepsia. Fesoterodine is contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma.
ChEBI: Fesoterodine is a diarylmethane.