| Indication |
For the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. |
| Pharmacodynamics |
Darifenacin is a competitive muscarinic receptor antagonist. In vitro
studies using human recombinant muscarinic receptor subtypes show that
darifenacin has greater affinity for the M3 receptor than for the other
known muscarinic receptors (9 and 12-fold greater affinity for M3
compared to M1 and M5, respectively, and 59-fold greater affinity for M3
compared to both M2 and M4). Muscarinic receptors play an important
role in several major cholinergically mediated functions, including
contractions of the urinary bladder smooth muscle and stimulation of
salivary secretion. Adverse drug effects such as dry mouth, constipation
and abnormal vision may be mediated through effects on M3 receptors in
these organs. |
| Mechanism of action |
Darifenacin selectively antagonizes the muscarinic M3 receptor. M3
receptors are involved in contraction of human bladder and
gastrointestinal smooth muscle, saliva production, and iris sphincter
function. |
| Absorption |
The mean oral bioavailability at steady state is estimated to be 15% and 19% for 7.5 mg and 15 mg tablets, respectively. |
| Volume of distribution |
|
| Protein binding |
Darifenacin is approximately 98% bound to plasma proteins (primarily to alpha-1-acid-glycoprotein). |
| Metabolism |
Hepatic. Primarily mediated by the cytochrome P450 enzymes CYP2D6 and CYP3A4. |
| Route of elimination |
Not Available |
| Half life |
The elimination half-life of darifenacin following chronic dosing is approximately 13-19 hours. |
| Clearance |
- 40 L/h [extensive metabolizers]
- 32 L/h [poor metabolizers]
|
| Toxicity |
Overdosage can potentially result in severe central anticholinergic effects. |
