Solifenacin pharmacology.
Antimuscarinics are the drugs of choice for the treatment of overactive bladder syndrome, and their benefit/risk ratio depends largely on selectivity for the different subtypes of muscarinic receptors. Solifenacin is the antimuscarinic that presents greatest selectivity for M3 bladder receptors, which may translate into a lower incidence of undesirable effects related to other receptor subtypes. Metabolic pathways of the antimuscarinics may impact efficacy and appearance of interactions. Solifenacin is metabolized only by the CYP3A4, giving three inactive metabolites and one with a similar activity to the original compound. However, other drugs in the group are also a substrate for the CYP 2D6 which presents polymorphisms, whereby their pharmacokinetics may be modified in slow metabolizers. The risk of interactions of solifenacin is low, and it is lower than that of the antimuscarinics which are also metabolized by the CYP 2D6. The unaltered fraction of solifenacin which is eliminated in urine, together with the active metabolite, can contribute to the therapeutic effect by acting on the urothelium receptors. It is not necessary to adjust doses of solifenacin in elderly patients or those with moderate liver or kidney impairment.
Departamento de Farmacología, Facultad de Medicina y Odontología, Universidad de Valencia, Avda. Blasco Ibáñez 15, Valencia, Spain. morales@uv.es
Francisco J
FJ
Morales-Olivas
Luis
L
Estañ
D000818:Animals; D006801:Humans; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011812:Quinuclidines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D053201:Urinary Bladder, Overactive / Q000188:drug therapy
D018727:Muscarinic Antagonists; D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; D000069464:Solifenacin Succinate