PHARMACOLOGY

PHARMACODYNAMICS

Tolterodine is a potent and competitive specific muscarinic receptor antagonist. Tolterodine acts on M₂ and M₃, subtypes of muscarinic receptors. It targets the bladder more than other areas of the body.  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.

Non-selectivity property of tolterodine offers more complete suppression of detrusor overactivity. The prevention of Ach binding with M3 receptor prevents bladder contraction due to decrease in cytosolic calcium whereas with M2 receptor causes relaxation.

 PHARMACOKINETIC

• Absorption: Tolterodine immediate release is rapidly absorbed, and maximum serum concentrations typically occur within 1 to 2 hours after dose administration with Bioavailability being 77 % . Food intake increases the bioavailability of tolterodine (average increase 53%)
• Distribution: Tolterodine is highly bound to plasma proteins, primarily α1-acid glycoprotein. The volume of distribution 113 ± 26.7 L
• Metabolism: Tolterodine is extensively metabolized by the liver following oral dosing. The primary metabolic route involves the oxidation of the 5-methyl group and is mediated by the cytochrome P450 2D6 (CYP2D6) and leads to the formation of a pharmacologically active 5-hydroxymethyl metabolite
• Elimination :  Half-life: Parent drug, 1.9-3.7 hr; active metabolite (5-hydroxymethyl), 3 hr (8.7 hr in cirrhosis); Total body clearance: 5.7 L/kg/hr; Excretion: Urine (77%), feces (17%).

PREGNANCY CATEGORY  : C