Solifenacin

362.46

362.46

A8910SQJ1U

DTXSID3048289

G04BD08|G - Genito urinary system and sex hormones

32.78000

3.74070

1.24±0.1 g/cm3

134-136

505.5±50.0 °C(Predicted)

259.5ºC

1.648

2.41E-10mmHg at 25°C

9.03±0.33

The LD50 of Solifenacin has yet to be determined. Signs of overdose include severe anticholinergic effects, mental status changes, and decreased consciousness. In case of overdose, treat patients with gastric lavage and supportive measures. Monitor patients with an ECG.

Like other anticholinergic agents, solifenacin has not been linked to episodes of liver enzyme elevations or clinically apparent liver injury. Solifenacin is metabolized in the liver via the cytochrome P450 system (CYP 3A4).

Solifenacin is 93-96% protein bound in plasma, mainly to alpha-1-acid glycoprotein.

Solifenacin tablets are indicated to treat an overactive bladder with urinary incontinence, urgency, and frequency.|FDA Label

Solifenacin is an anticholinergic and antispasmodic agent used to treat urinary incontinence and the overactive bladder syndrome. Solifenacin has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury.

Anticholinergic Agents

Solifenacin antagonizes the M2 and M3 muscarinic receptors in the bladder to treat an overactive bladder. It has a long duration of action as it is usually taken once daily. Patients taking solifenacin should be aware of the risks of angioedema and anaphylaxis.

Drugs used in the treatment of urogenital conditions and diseases such as URINARY INCONTINENCE; PROSTATIC HYPERPLASIA; and ERECTILE DYSFUNCTION. (See all compounds classified as Urological Agents.)|Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. (See all compounds classified as Muscarinic Antagonists.)

Solifenacin is well absorbed in the duodenum, jejunum, and ileum but not the stomach. Absorption occurs via passive diffusion and so no transporters are involved. The mean oral bioavailability of solifenacin is 88%. The T_max of solifenacin is 3-8 hours with a C_ss of 32.3ng/mL for a 5mg oral dose and 62.9ng/mL for a 10mg oral dose.|69.2±7.8% of a radiolabelled dose is recovered in the urine, 22.5±3.3% was recovered in feces, and 0.4±7.8% was recovered in exhaled air. 18% of solifenacin is eliminated as the N-oxide metabolite, 9% is eliminated as the 4R-hydroxy N-oxide metabolite, and 8% is eliminated as the 4R-hydroxy metabolite.|The volume of distribution of solifenacin is 600L.|The clearance of solifenacin is 7-14L/h and a renal clearance of 0.67-1.51L/h.

Solifenacin undergoes N-oxidation at the quinuclidin ring by cytochrome P450, though the exact enzymes are not revealed in the literature. The tetrahydroisoquinolone ring is 4R-hydroxylated by CYP3A4, CYP1A1, and CYP2D6. A 4R-hydroxy N-oxide metabolite is also formed by CYP3A4. Finally, solifenacin can undergo direct glucuronidation. Only solifenacin and the 4R-hydroxy metabolite are pharmacologically active.

The elimination half life of solifenacin ranges from 33-85 hours.

Solifenacin is a competitive muscarinic receptor antagonist. It has the highest affinity for M3, M1, and M2 muscarinic receptors. 80% of the muscarinic receptors in the bladder are M2, while 20% are M3. Solifenacin's antagonism of the M3 receptor prevents contraction of the detrusor muscle, while antagonism of the M2 receptor may prevent contraction of smooth muscle in the bladder.

2(1H)-Isoquinolinecarboxylic acid, 3,4-dihydro-1-phenyl-,1- azabicyclo(2.2.2)oct-3-yl ester, (R-(R*,S*))-

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients