Urispas 200 Mechanism of Action

Pharmacology: Pharmacodynamics: Flavoxate hydrochloride (and its main metabolite methyl flavone carboxylic acid, MFCA) is an antispasmodic selective to the urinary tract. In animal and human studies, flavoxate hydrochloride has been shown to have a direct antispasmodic action on smooth muscle fibres.
The mechanism of action involves intracellular cyclic AMP accumulation and calcium blocking activity. It inhibits bladder contractions induced by various agonists or by electrical stimulation and inhibits the frequency of bladder voiding contractions. It increases bladder volume capacity, reduces the threshold pressure and micturition pressure.
In addition, animal studies have shown flavoxate hydrochloride to have analgesic and local anaesthetic properties.
Flavoxate does not significantly affect cardiac or respiratory functions.
Pharmacokinetics: Oral studies in man have indicated that flavoxate is readily absorbed from the intestine and converted, to a large extent, almost immediately to MFCA.
Following an IV dose (equimolar to 100mg), the following parameters were calculated for flavoxate: T1/2 83.3 mins: apparent volume of distribution 2.89 l/kg. The apparent distribution of MFCA was 0.20 l/kg. No free flavoxate was found in urine (24 hours). However, 47% of the dose was excreted as MFCA.
Following single oral dosing to volunteers of 200mg and 400mg flavoxate, almost no free flavoxate was detected in the plasma. The peak level of MFCA was attained at 30-60 mins after the 200mg dose and at around two hours following the 400mg dose. The AUC for the 400mg dose was approximately twice as large as the AUC for the 200mg dose. About 50% of the dose was excreted as MFCA within 12 hours; most being excreted within the first 6 hours.
After repeated oral dosing (200 mg, TDS, 7 days) the cumulative excretion of metabolites stabilised at 60% of the dose on the third day remaining almost unchanged after one week.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and toxicity to reproduction and development. Carcinogenicity studies have not been performed.