化合物信息

Drug Groups

approved

Description

Solifenacin (rINN), marketed as solifenacin succinate under the trade name Vesicare, is a urinary antispasmodic of the anticholinergic class. It is used in the treatment of overactive bladder with urge incontinence. [Wikipedia]

Indication

For the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.

Pharmacology

Solifenacin is a competitive muscarinic receptor antagonist. Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of urinary bladder smooth muscle and stimulation of salivary secretion.

Toxicity

Overdosage with solifenacin can potentially result in severe anticholinergic effects and should be treated accordingly. The highest solifenacin dose given to human volunteers was a single 100 mg dose. Intolerable anticholinergic side effects (fixed and dilated pupils, blurred vision, failure of heel-to-toe exam, tremors and dry skin) occurred on day 3 in normal volunteers taking 50 mg daily (5 times the maximum recommended therapeutic dose).

Affected Organisms

Biotransformation

Solifenacin is extensively metabolized in the liver. The primary pathway for elimination is by way of CYP3A4; however, alternate metabolic pathways exist. The primary metabolic routes of solifenacin are through N-oxidation of the quinuclidin ring and 4R-hydroxylation of tetrahydroisoquinoline ring. One pharmacologically active metabolite (4R-hydroxy solifenacin), occurring at low concentrations and unlikely to contribute significantly to clinical activity, and three pharmacologically inactive metabolites (N-glucuronide and the N-oxide and 4R-hydroxy-N-oxide of solifenacin) have been found in human plasma after oral dosing.

Absorption

The absolute bioavailability of solifenacin is approximately 90%, and plasma concentrations of solifenacin are proportional to the dose administered.

Half Life

The elimination half-life of solifenacin following chronic dosing is approximately 45-68 hours.

Protein Binding

Solifenacin is approximately 98% (in vivo) bound to human plasma proteins, principally to alpha1-acid glycoprotein.

Elimination

The primary pathway for elimination is by way of CYP3A4; however, alternate metabolic pathways exist.

Distribution

* 600 L

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