| Indication |
For the treatment of overactive bladder (with symptoms of urinary frequency, urgency, or urge incontinence). |
| Pharmacodynamics |
Tolterodine is a competitive muscarinic receptor antagonist.
Both urinary bladder contraction and salivation are mediated via
cholinergic muscarinic receptors. After oral administration, tolterodine
is metabolized in the liver, resulting in the formation of the
5-hydroxymethyl derivative, a major pharmacologically active metabolite.
The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic
activity similar to that of tolterodine, contributes significantly to
the therapeutic effect. Both tolterodine and the 5-hydroxymethyl
metabolite exhibit a high specificity for muscarinic receptors, since
both show negligible activity or affinity for other neurotransmitter
receptors and other potential cellular targets, such as calcium
channels. Tolterodine has a pronounced effect on bladder function. The
main effects of tolterodine are an increase in residual urine,
reflecting an incomplete emptying of the bladder, and a decrease in
detrusor pressure, consistent with an antimuscarinic action on the lower
urinary tract. |
| Mechanism of action |
Both tolterodine and its active metabolite,
5-hydroxymethyltolterodine, act as competitive antagonists at muscarinic
receptors. This antagonism results in inhibition of bladder
contraction, decrease in detrusor pressure, and an incomplete emptying
of the bladder. |
| Absorption |
Not Available |
| Volume of distribution |
|
| Protein binding |
Approximately 96.3%. |
| Metabolism |
Not Available |
| Route of elimination |
Following administration of a 5-mg oral dose of 14C-tolterodine
solution to healthy volunteers, 77% of radioactivity was recovered in
urine and 17% was recovered in feces in 7 days. |
| Half life |
1.9-3.7 hours |
| Clearance |
Not Available |
| Toxicity |
Not Available |
