Disease relevance of Propiverine

• PURPOSE: We evaluated the efficacy and safety of a therapeutic modality involving propiverine combined with doxazosin in patients with overactive bladder (OAB) and benign prostatic obstruction [1].
• The study investigated the efficacy and cardiac safety of propiverine in the elderly, because the induction of life-threatening ventricular arrhythmia has been reported for some drugs prescribed in the therapy of urinary incontinence [2].
• METHODS: Thus, we performed a study to examine whether oxybutynin, pentoxyverine and etafenone, as well as propiverine, induce catalepsy in mice [3].
• Propiverine-induced Parkinsonism: a case report and a pharmacokinetic/pharmacodynamic study in mice [3].
• Pharmacokinetics and safety of propiverine in patients with fatty liver disease [4].

High impact information on Propiverine

• 3. Atropine, propiverine and M-6 significantly shifted the cumulative concentration-response curves for carbachol (CCh) to higher concentrations [5].
• PURPOSE: We examined the mechanism involved in the inhibition of bladder activity in rats by stimulating the rostral pontine reticular formation (RPRF) using carbachol, flavoxate and propiverine, and by analysis of amino acid levels in the lumbosacral cord [6].
• Intravenous injection of flavoxate or propiverine (0.1 to 10 mg/kg each) inhibited bladder contraction [6].
• These results were confirmed for propiverine in human detrusor smooth muscle cells (hDSMC) [7].
• Chronic propiverine treatment reduced hepatic and intestinal CYP3A4 activity slightly to 0.89-fold and 0.80-fold, respectively [90% confidence interval (CI) for test/reference ratios 0.85-0.93 and 0.72-0.89], with the combined effect resulting in a 1.46-fold increase in area under the curve of oral midazolam (90% CI 1.36-1.57) [8].

Chemical compound and disease context of Propiverine

• Antagonists of muscarinic acetylcholine receptors, such as darifenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium, are the mainstay of the treatment of the overactive bladder syndrome [9].
• RESULTS: The intensity of drug-induced catalepsy was in the order: haloperidol > etafenone > pentoxyverine > propiverine > oxybutynin [3].

Biological context of Propiverine

• OBJECTIVE: The present study was designed to assess the pharmacokinetics of propiverine after single and multiple dosing in patients with and without fatty liver disease [4].
• RESULTS: No significant differences were observed for propiverine and its main metabolite with regard to peak serum concentration (Cmax), area under the serum concentration-time curve (AUC) and elimination half-life (t1/2) [4].
• Quantification of propiverine by liquid chromatography/electrospray tandem mass spectrometry: application to a bioequivalence study of two formulations in healthy subjects [10].
• Clinical and urodynamic effects of propiverine in patients suffering from urgency and urge incontinence. A multicentre dose-optimizing study [11].
• Treatment with propiverine 45 mg resulted in the highest rates of constipation, lengthening of the visual near point, and effects on heart rate [12].

Anatomical context of Propiverine

• In this study, we compared the effectiveness of propiverine hydrochloride (propiverine) and oxybutynin chloride (oxybutynin) on the increased urinary frequency and cognitive impairment induced by nucleus basalis magnocellularis (nBM) lesioning in conscious and nonrestrained rats [13].
• Similarly, oral administration of propiverine at doses of 74.3-297 micromol/kg brought about a significant increase in the Kd values for (-)-[3H]QNB binding in rat tissues including the bladder, and greater increase in Kd values was seen in the rat prostate, heart and submaxillary gland [14].
• AIMS OF THE STUDY: The aim of this double-blind, randomised, prospective, multicentre trial was to evaluate the efficacy of propiverine in patients suffering from detrusor hyperreflexia caused by spinal cord injury in comparison to placebo [15].

Associations of Propiverine with other chemical compounds

• In muscle strips isolated from guinea-pig and rat urinary bladder, propiverine (3-10 microM) inhibited carbachol-induced contractions in the presence of verapamil and Ca(2+)-induced contractions in excess K+ medium containing atropine, suggesting it has both anticholinergic and Ca2+ channel blocking actions [16].
• METHODS: In a randomised, double-blind, multicentre clinical trial, patients with idiopathic detrusor overactivity were treated with 15 mg propiverine twice daily or 2mg tolterodine twice daily over a period of 28 days [17].
• Comparison of the in vitro skin penetration of propiverine with that of terodiline [18].
• In these in vitro studies, the antimuscarinic action of solifenacin was more potent than that of propiverine and less potent than those of tolterodine, oxybutynin, darifenacin and atropine [19].

Gene context of Propiverine

• Propiverine had no relevant effect on CYP2C9, CYP2C19, and CYP1A2 (90% CI for test/reference ratios 0.93-1.00, 0.84-0.96, and 0.97-1.07, respectively) [8].
• Results show that Propiverine induced several monooxygenases and CYP2B expression dose dependently [20].
• Furthermore, the inhibitory potency of propiverine on P450 enzymes was evaluated in competition assays with three most specific monooxygenases [20].
• Influence of propiverine on hepatic microsomal cytochrome p450 enzymes in male rats [20].
• In man propiverine is bound to serum albumin at a single site with high affinity (KA1 = 1.45 x 10(4) L mol-1) and at least two sites with low affinity (KA2 = 2.5 x 10(2) L mol-1) [21].

Analytical, diagnostic and therapeutic context of Propiverine

• CONCLUSION: No pharmacokinetic differences relevant for safety were observed, comparing patients with and without fatty liver disease following repeated oral administration of propiverine [4].
• A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence [22].
• A pharmacokinetic study with 30 mg propiverine p.o. was performed in healthy volunteers (10 males, 6 females, age 36-56 years, body weight 55-100 kg, body height 162-184 cm, Broca index 0.96-1.19) [23].
• Byakko-ka-ninjin-to (BN) is a Kampo medicine (traditional Japanese medicine) that is frequently used to treat xerostomia, which is also a side effect of anticholinergic agents such as oxybutynin and propiverine widely used for the treatment of patients with urinary incontinence or frequency [24].

References