By preventing the binding of acetylcholine to these receptors, solifenacin reduces smooth muscle tone in the bladder, allowing the bladder to retain larger volumes of urine and reducing the number of micturition, urgency and incontinence episodes. Because of a long elimination half life, a once-a-day dose can offer 24-hour control of the urinary bladder smooth muscle tone. Pharmacokinetics
Peak plasma concentrations are reached three to eight hours after absorption from the gut. In the bloodstream, 98% of the substance are bound to plasma proteins, mainly acidic ones. Metabolism is mediated by the liver enzyme CYP3A4 and possibly others. There is one known active metabolite, 4R-hydroxysolifenacin, and three inactive ones, the N-glucuronide, the N-oxide and the 4R-hydroxy-N-oxide. The elimination half-life is 45 to 68 hours. 69% of the substance, both in its original form and as metabolites, are excreted renally and 23% via the feces. Chemistry
Like other anticholinergics, solifenacin is an ester of a carboxylic acid containing (at least) an aromatic ring with an alcohol containing a nitrogen atom. While in the prototype anticholinergic atropine the bicyclic ring is tropane, solifenacin replaces it with quinuclidine. The free base is a yellow oil, while the salt solifenacin succinate forms yellowish crystals. History
The compound was studied using animal models by the Yamanouchi Pharmaceutical Co., Ltd. of Tokyo, Japan.
Pharmacology
Mechanism of Action
Oxacillin, through its β-lactam ring, covalently binds to penicillin-binding proteins, which are enzymes involved in the synthesis of the bacterial cell wall. This binding interaction interferes with the transpeptidation reaction and inhibits the synthesis of peptidoglycan, a prominent component of the cell wall. By decreasing the integrity of the bacterial cell wall, it is thought that oxacillin and other penicillins kill actively growing bacteria through cell autolysis. Chemistry
As with other members of the penicillin family, the chemical structure of oxacillin features a 6-aminopenicillanic acid nucleus with a substituent attached to the amino group. The 6-aminopenicillanic acid nucleus consists of a thiazolidine ring attached to a β-lactam ring, which is the active moiety responsible for the antibacterial activity of the penicillin family. The substituent present on oxacillin is thought to impart resistance to degradation via bacterial β-lactamases. History
Oxacillin, a derivative of methicillin, was first synthesized in the early 1960s as part of a research initiative led by Peter Doyle and John Naylor of Beecham, in consort with Bristol-Myers. Members of the isoxazolyl penicillin family, which includes cloxacillin, dicloxacillin, and oxacillin, were synthesized to counter the increasing prevalence of infections caused by penicillin-resistant Staphylococcus aureus. While methicillin could only be administered via injection, the isoxazolyl penicillins, including oxacillin, could be given orally or by injection. Following the synthesis of cloxacillin and oxacillin, Beecham retained the right to commercially develop cloxacillin in the United Kingdom while Bristol-Myers was given the marketing rights for oxacillin in the United States.