In vitro and in vivo tissue selectivity profile of solifenacin succinate (YM905) for urinary bladder over salivary gland in rats

Ohtake, Akiyoshi; Ukai, Masashi; Hatanaka, Toshiki; Kobayashi, Seiji; Ikeda, Ken; Sato, Shuichi; Miyata, Keiji; Sasamata, Masao

doi:10.1016/j.ejphar.2004.03.044

Cited by 115 publications

(94 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Solifenacin inhibited carbachol-induced increases in intracellular Ca 2+ levels in bladder smooth muscle cells and salivary gland cells isolated from rats in a concentration-dependent manner (14,15). The inhibitory potency for bladder smooth muscle cells was significantly greater than that for submandibular gland cells.…”

Section: Bladder-selectivity Profile 231 In Vitromentioning

confidence: 99%

See 1 more Smart Citation

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

et al. 2010

Self Cite

View full text Add to dashboard Cite

Abstract. Overactive bladder (OAB) syndrome is a common condition that is most often observed in the elderly. Pharmacological treatment with muscarinic receptor antagonists has been most widely used for OAB. An antimuscarinic agent, solifenacin, showed the highest affinity for the muscarinic M 3 receptor, which mediates urinary bladder contraction. In preclinical studies, solifenacin exhibited a highly bladder-selective profile compared with other antimuscarinic agents. Solifenacin was also shown to increase bladder capacity without affecting residual urine in an OAB model of rats. Urgency is now considered to result from overactivation of afferent nerves from the urinary bladder. It has been reported that afferent nerves are located adjacent to the urothelium, and stimulation of muscarinic receptors expressed on the urothelium may contribute to the activation of afferent nerves via non-neuronal ATP release. Solifenacin produces its inhibitory effect on bladder afferent activity partly via the suppression of non-neuronal ATP release. Clinically, solifenacin ameliorates all symptoms in OAB patients; and in particular, it produces a significant decrease in urgency episodes, which is the principal symptom of OAB. The pharmacological profile of solifenacin is therefore considered to contribute to its beneficial effects of high efficacy against OAB symptoms with good tolerability.

show abstract

Section: Bladder-selectivity Profile 231 In Vitromentioning

confidence: 99%

“…The effects of antimuscarinic agents on carbachol-induced increases in intravesical pressure and salivary secretion were investigated in anesthetized rats (14,15).…”

Section: In Vivomentioning

confidence: 99%

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…The inhibitory effect of solifenacin on carbachol-stimulated Ca 2+ mobilization was as potent as that of oxybutynin in detrusor cells, but 6 -25 times weaker in submandibular gland cells (32,33). In vivo studies in anesthetized rats have shown that solifenacin was 4 -7 times more potent in inhibiting bladder contraction than salivation, whereas oxybutynin had little bladder selectivity (32,34). Thus, solifenacin may exhibit pharmacological selectivity in the bladder relative to other tissues such as the salivary gland.…”

Section: Solifenacinmentioning

confidence: 95%

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Bladder Selectivity Based on In Vivo Drug–Receptor Binding Characteristics of Antimuscarinic Agents for Treatment of Overactive Bladder

et al. 2010

View full text Add to dashboard Cite

Abstract.We have reviewed the binding of antimuscarinic agents, used to treat urinary dysfunction in patients with overactive bladder, to muscarinic receptors in target and non-target tissues in vivo. Transdermal administration of oxybutynin in rats led to significant binding in the bladder without long-term binding in the submaxillary gland and the abolishment of salivation evoked by oral oxybutynin. Oral solifenacin showed significant and long-lasting binding to muscarinic receptors in mouse tissues expressing the M 3 subtype. Oral tolterodine bound more selectively to muscarinic receptors in the bladder than in the submaxillary gland in mice. The muscarinic receptor binding activity of oral darifenacin in mice was shown to be pronounced and long-lasting in the bladder, submaxillary gland, and lung. In vivo quantitative autoradiography using (+) N -[11 C] methyl-3-piperidyl benzilate in rats showed significant occupancy of brain muscarinic receptors on intravenous injection of oxybutynin, propiverine, solifenacin, and tolterodine. The estimated in vivo bladder selectivity compared to brain was significantly greater for solifenacin and tolterodine than oxybutynin. Darifenacin occupied few brain muscarinic receptors. Similar findings were also observed with positron emission tomography in conscious rhesus monkeys. The newer generation of antimuscarinic agents may be advantageous in the bladder selectivity after systemic administration.

show abstract

“…Solifenacin succinate is a once-daily, muscarinic receptor antagonist, showing tissue preference for the bladder over the salivary gland in animal models (15,16). Solifenacin has been shown in clinical studies to produce statistically significant improvements in all symptoms of OAB (17 -20).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, Safety, and Tolerability of Solifenacin in Patients With Renal Insufficiency

et al. 2007

View full text Add to dashboard Cite

Abstract. To evaluate the pharmacokinetics, safety, and tolerability of solifenacin in patients with mild, moderate, or severe renal disease, eighteen patients with renal disease and six healthy volunteers received a single oral dose of solifenacin (10 mg). Pharmacokinetic parameters were assessed from blood samples drawn over a 360-h period. Safety and tolerability were also evaluated. Total mean ± S.D. exposure (ng ⋅ h / mL) to solifenacin in healthy individuals (1190 ± 403) was increased in patients with renal disease (mild: 1784 ± 792, moderate: 1559 ± 555, severe: 2530 ± 700), and elimination half-life (mean ± S.D.[h]) was prolonged (healthy: 68.2 ± 27.2, mild: 89.1 ± 34.5, moderate: 90.6 ± 27.3, severe: 111 ± 38.3). A significant correlation was found between creatinine clearance and pharmacokinetic parameters for exposure and apparent oral clearance. No deaths or serious adverse events occurred during the study. Solifenacin 10 mg was well tolerated in patients with renal disease. Solifenacin displays a higher exposure and a prolonged half-life in patients with renal impairment, especially severe. Therefore, while no special cautions are necessary for patients with mild / moderate renal impairment, patients with severe renal impairment should receive no more than 5 mg solifenacin once daily.

show abstract

In vitro and in vivo tissue selectivity profile of solifenacin succinate (YM905) for urinary bladder over salivary gland in rats

Cited by 115 publications

References 20 publications

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Bladder Selectivity Based on In Vivo Drug–Receptor Binding Characteristics of Antimuscarinic Agents for Treatment of Overactive Bladder

Pharmacokinetics, Safety, and Tolerability of Solifenacin in Patients With Renal Insufficiency

Contact Info

Product

Resources

About