Propiverine

367.5 g/mol

367.48

468GE2241L

DTXSID5048265

G - Genito urinary system and sex hormones

38.8 Ų

224-226

484.2

5mg/mL

The most common adverse reactions reported in patients treated with propiverine include dry mouth, headache, accommodation disorder, constipation, abdominal pain, dyspepsia and fatigue. Propiverine may cause drowsiness and blurred vision. This may impair the ability to exert activities that require mental alertness such as operating a motor vehicle or other machinery, or to perform hazardous work while taking this drug. There have been reports of QT interval prolongation with antimuscarinic medications in the same class of drugs of propiverine hydrochloride. Some drugs that may cause QT/QTc interval prolongation may increase the risk of a rare, but serious ventricular arrhythmia called _torsades de pointes_. Patients at risk for QT/QTc interval prolongation, such as those with diagnosed heart failure, long QT syndrome, recent significant hypokalemia episodes or receiving other drugs known to prolong QT/QTc, should be closely monitored while treated with propiverine. Patients who experience prolonged QT/QTc or symptoms of possible arrhythmias including dizziness, palpitations or fainting should be electrocardiographically evaluated and monitored for electrolyte disturbances. Propiverine, like other anticholinergics, induces mydriasis. Therefore, the risk to induce acute angle-closure glaucoma in individuals predisposed with narrow angles of the anterior chamber may be increased. Drugs of this class, including propiverine, have been reported to induce or precipitate acute angle-closure glaucoma. No clinical data are available on the use of propiverine in pregnant women. Studies in animals have shown reproductive toxicity.

90-95% for the parent compound and about 60% for the main metabolite.

Indicated for symptomatic treatment of urinary incontinence and/or increased urinary frequency and urgency in patients with overactive bladder (OAB). Propiverine may also be used in patients with neurogenic bladder as a result of spinal cord injury.

Propiverine hydrochloride inhibits abnormal contractions of bladder smooth muscle in vivo through not only its anticholinergic activity but also its concurrent calcium antagonistic activity. Through the above-mentioned mechanism, propiverine is able to relieve the symptoms of overactive bladder. In animal models, this administration of this drug leads to a dose-dependent decrease in intravesical pressure of the bladder and an increase in bladder capacity. In patients with symptoms of OAB resulting from idiopathic detrusor muscle overactivity (IDO) or neurogenic detrusor overactivity (NDO), propiverine showed dose-dependent efficacy and tolerability.

Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. (See all compounds classified as Muscarinic Antagonists.)|Drugs used in the treatment of urogenital conditions and diseases such as URINARY INCONTINENCE; PROSTATIC HYPERPLASIA; and ERECTILE DYSFUNCTION. (See all compounds classified as Urological Agents.)|Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS. (See all compounds classified as Parasympatholytics.)

Propiverine is rapidly absorbed from the gastrointestinal tract with maximum plasma concentrations attained after 2.3 hours. the mean absolute bioavailability of mictonorm 15 mg tablets (propiverine) is 40.5 %. It undergoes heavy first-pass metabolism in the liver.|Following the ingestion of 30 mg propiverine, 60% radioactivity was recovered in urine and 21% was recovered in feces within 12 days. Less than 1% of an oral dose is excreted unchanged in the urine.|In one study, the volume of distribution was calculated in 21 healthy volunteers after intravenous (IV) administration of propiverine hydrochloride was measured to range from 125 to 4731 (average 2791) indicating, that a large amount of available propiverine is distributed to peripheral compartments.|Mean total clearance after single dose administration of 30 mg is 371 mL/min (191 – 870 mL/min).

The major metabolites were found to be as follows; 4-piperidyl diphenylpropoxyacetate (DM-P-4), 1-methyl-4-piperidyl benzilate (Dpr-P-4) and 1-methyl-4-piperidyl diphenyl-(2 carboxy) ethoxyacetate (ω-COOH-P-4) in the liver, Dpt-p-4, DM-P-4 in the kidney, and DM-P-4, DPr-P-4 in the lung. In the same pharmacokinetic study, All pharmacologically active compounds such as the unchanged compound, 1-methyl-4-piperidyl benzilate N-oxide (DPr-P-4 (N→O)), Dpt-p-4 and 1-methyl-4-piperidyl diphenylpropoxyacetate N-oxide (P-4 (N→O)) were present in the urinary bladder, a target organ for P-4, at higher concentrations than in the plasma. Propiverine is metabolized by both intestinal and hepatic enzymes. The main metabolic pathway involves the oxidation of the _piperidyl-N _and is mediated by _CYP 3A4_ and _flavin-containing monooxygenases (FMO) _1 and 3 and results in the formation of the second main metabolite M-5, the plasma concentration of which is greater in concentration that of the parent substance propiverine. Four metabolites have been identified in the urine following propiverine ingestion; 3 them are pharmacologically active metabolites that may contribute to its therapeutic effect (M-5, M-6, M-23). The mean absolute bioavailability of propiverine IR 15 mg is 40.5%.

In three studies including a total of 37 healthy volunteers mean elimination half-life was 14.1, 20.1 and 22.1 hours, respectively.

Propiverine demonstrates both anticholinergic and calcium-modulating properties. The efferent connection of the pelvic nerve is inhibited due to the anticholinergic action exerted by this drug, leading to relaxation of bladder smooth muscle. Propiverine blocks calcium ion influx and modulates the intracellular calcium in urinary bladder smooth muscle cells, resulting in the inhibition of muscle spasm. The bladder contains several muscarinic receptors. Acetylcholine is the main contractile neurotransmitter in the human bladder detrusor muscle, and antimuscarinics such as propiverine exert their effects by competitively inhibiting the binding of acetylcholine at muscarinic receptors on detrusor smooth muscle cells and other structures within the bladder wall. In one study, After oral treatment with propiverine, the bladder showed the highest concentration of M-2, indicating a targeted distribution of this metabolite into the bladder. Therefore, muscarinic receptor-2 may highly contribute to the relatively selective and long-lasting occupation of bladder muscarinic receptors after oral ingestion of propiverine.

alpha-diphenyl alpha-n-propoxyacetic acid-4(1-methylpiperidyl)ester