Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Solifenacin Succinate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2007

Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents.

Solifenacin succinate [YM905; (3R)-1-azabicyclo[2.2.2]oct-3-yl(1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate monosuccinate] is a new muscarinic receptor antagonist developed for the treatment of overactive bladder. The aim of the present study was to evaluate the antimuscarinic properties of solifenacin and to compare the results with those obtained for tolterodine, oxybutynin, darifenacin, propiverine and atropine. In radioligand receptor binding assay, Ki values of solifenacin for human muscarinic M1, M2, M3, M4 and M5 receptors were 26, 170, 12, 110 and 31 nM, respectively. In isolated rat urinary bladder, solifenacin competitively antagonized carbachol-induced contractions, with a pA2 value of 7.44+/-0.09. 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. In anesthetized rats, solifenacin and oxybutynin increased the maximum bladder capacity in a dose-dependent manner and also decreased the maximum intravesical pressure. The dosages required to produce a 30% increase in maximum bladder capacity (ED30 values) of solifenacin and oxybutynin were 0.35 and 0.30 mg/kg i.v., respectively, indicating approximately equal efficacies. These results support the fact that solifenacin, similarly to currently used antimuscarinic agents, is an effective agent in the treatment of overactive bladder symptoms such as urinary frequency and urge incontinence.

Animals↗
PubMed2005

Muscarinic receptor binding, plasma concentration and inhibition of salivation after oral administration of a novel antimuscarinic agent, solifenacin succinate in mice.

1 A novel muscarinic receptor antagonist, solifenacin succinate, inhibited specific binding of [N-methyl-(3)H]-scopolamine ([(3)H]-NMS) in the mouse bladder, submaxillary gland and heart in a concentration-dependent manner. This inhibitory effect was greatest in the submaxillary gland, followed by the bladder and heart. 2 After oral administration of oxybutynin (76.1 micromol kg(-1)) or solifenacin (62.4, 208 micromol kg(-1)), a significant dose- and time-dependent increase in K(D) values for specific [(3)H]-NMS binding was seen in the bladder, prostate, submaxillary gland, heart, colon and lung, compared with control values. The increase in K(D) induced by oxybutynin in each tissue reached a maximum 0.5 h after oral administration and then rapidly declined, while that induced by solifenacin was greatest 2 h after administration and was maintained for at least 6 or 12 h, depending on the dose. The muscarinic receptor binding of oral solifenacin was slower in onset and of a longer duration than that of oxybutynin. 3 Plasma concentrations of oxybutynin and its active metabolite (N-desethyl-oxybutynin, DEOB) were maximum 0.5 h after its oral administration and then declined rapidly. Oral solifenacin persisted in the blood for longer than oxybutynin. 4 Pilocarpine-induced salivary secretion in mice was significantly reduced by oral administration of solifenacin and was completely abolished 0.5 h after oral oxybutynin. Although the suppression induced by solifenacin was more persistent than that due to oxybutynin, the antagonistic effect of solifenacin on the dose-response curves to pilocarpine was significantly weaker than that of oxybutynin. It is concluded that oral solifenacin persistently binds to muscarinic receptors in tissues expressing the M(3) subtype, such as the bladder.

Administration, Oral↗
PubMed2004

Pharmacokinetics and safety of solifenacin succinate in healthy young men.

The pharmacokinetic profile of solifenacin succinate (YM905; Vesicare), a new once-daily bladder-selective muscarinic receptor antagonist, was examined in 2 controlled trials of healthy young men. A single-dose study evaluated 5-, 10-, 20-, 40-, 60-, 80-, and 100-mg doses. A multidose study evaluated 5-, 10-, 20-, and 30-mg doses. In the single-dose study, mean time to maximal concentration and elimination half-life ranged from 3.3 to 4.8 and from 40.2 to 57.6 hours, respectively; in the multidose study, the corresponding ranges were 2.9 to 5.8 and 45.0 to 64.8. Plasma concentration and area under the curve increased linearly with single doses in both trials. At steady state, a less regular increase was seen, with higher values in the 20-mg group than in the 30-mg group. All doses in the single-dose study were well tolerated. At steady state, only the 30-mg dose was not well tolerated. The most commonly reported adverse events were dry mouth, blurred vision, and headache. Solifenacin 5 and 10 mg, either as single doses or at steady state, had minimal effect on salivary flow, visual nearpoint, and the incidence of adverse events. Solifenacin was well tolerated up to single doses of 100 mg and after multiple doses of 20 mg. Its pharmacokinetic profile makes it suitable for qd administration.

Adolescent↗
PubMed2005

Effects of solifenacin succinate (YM905) on detrusor overactivity in conscious cerebral infarcted rats.

Solifenacin succinate [YM905, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] is a novel muscarinic receptor antagonist. We examined the effects of solifenacin and two other muscarinic receptor antagonists, tolterodine and propiverine, on detrusor overactivity in cerebral infarcted rats. Evaluation was done under conscious conditions using cystometry 1 day after middle cerebral artery occlusion. The cerebral infarcted rats showed decreases in bladder capacity and voided volume and an increase in residual volume, but no change in micturition pressure. Solifenacin increased bladder capacity and voided volume at doses of 0.03 mg/kg i.v. or more. Tolterodine increased bladder capacity and voided volume at 0.03 and 0.1 mg/kg i.v., while propiverine increased bladder capacity and voided volume at 1 mg/kg i.v. and at 0.3 and 1 mg/kg i.v., respectively. In contrast, none of the three drugs affected residual volume or micturition pressure. These results suggest that solifenacin may improve detrusor overactivity without causing urinary retention and may be a promising drug in the treatment of patients with overactive bladder syndrome.

Animals↗
PubMed2004

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

Solifenacin succinate [YM905; (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] is a new muscarinic receptor antagonist developed for the treatment of overactive bladder. The aim of the present study was to evaluate the in vitro and in vivo bladder selectivity profile of solifenacin over salivary gland in the same animal species, and to compare the results with those obtained for tolterodine, oxybutynin, darifenacin and atropine. Solifenacin and the other antimuscarinic drugs 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. The inhibitory effect of solifenacin for bladder smooth muscle cells (pK(i)=8.12) was 3.6-fold more potent than that for salivary gland cells (pK(i)=7.57). In contrast, the inhibitory effects of the other antimuscarinic drugs for bladder smooth muscle cells were 1.7- to 2.2-fold more potent than those for salivary gland cells. In anesthetized rats, solifenacin dose-dependently inhibited carbachol-induced intravesical pressure elevation and salivary secretion, and exhibited functional selectivity (3.7- to 6.5-fold) for urinary bladder over salivary gland. Tolterodine was also 2.2- to 2.4-fold more selective in inhibition of bladder response. In contrast, oxybutynin, darifenacin and atropine did not show functional selectivity for urinary bladder. These results indicate that solifenacin exerts greater selectivity for urinary bladder over salivary gland than tolterodine, oxybutynin, darifenacin and atropine, and may consequently provide symptomatic benefit in the treatment of overactive bladder with less dry mouth than currently used antimuscarinic drugs.

Animals↗
PubMed2007

Comparison of the efficacy and tolerability of solifenacin succinate with or without previous use of trospium chloride.

Overactive bladder syndrome (OBS) is described as urinary urgency with or without incontinence, usually with increased daytime frequency and nocturia in the absence of another identifiable pathological process. Nowadays and despite other alternative therapies, the mainstay of OBS is still the pharmacological approach, mainly with anti-muscarinic drugs. To compare the efficacy of a 30-day solifenacin succinate (5 mg OD) treatment with or without previous medication with trospium chloride, a prostective open, two-arm, parallel group study was conducted for 5 weeks in 40 patients with OBS. The primary endpoint was patient self-assessment of improvement after 30 days of medication. Secondary endpoints included the reduction of the daily number of voids and urgency or involuntary leakage episodes. Adverse reactions and therapeutic stoppage were also evaluated. To be included in the trospium chloride treatment group, patients were required to have been treated with such drug for 1 to 6 months before the present study. Evaluation and efficacy assessment were accomplished using a 3-day bladder diary and an urgency severity scale (USS). Safety assessment was done by recording all the patients' complaints after starting medication. A total of 40 patients were enrolled for this study, 19 without previous medication and 21 who had already tried trospium chloride. Two patients from the non-previous medication group were excluded. Globally, there was a statistically significant reduction for the USS (2.73-->1.73), the daily number of voids (9.5-->7.0), of urgency episodes (9.1-->4.0) and of involuntary leakage episodes (3.6-->1.0) over the 24 h. Six patients had no improvement, four from the previous trospium chloride group and two from the non-previous medication group. Three patients reported side effects, two cases of dry mouth and one case of constipation. One patient dropped out of the treatment due to an unspecified intolerance. Solifenacin succinate 5 mg seems to be effective concerning patients' self-assessment of improvement and decrease in the mean number of daily voids, urgency episodes and incontinence episodes. This was reported both in patients who have already been medicated with trospium chloride and those who have never taken any kind of medication. Regarding side effects, solifenacin is quite well-tolerated in both groups.

Aged↗
PubMed2004

Comparison of in vitro selectivity profiles of solifenacin succinate (YM905) and current antimuscarinic drugs in bladder and salivary glands: a Ca2+ mobilization study in monkey cells.

We investigated the effects of the new muscarinic receptor antagonist solifenacin succinate [YM905; (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] and the current antimuscarinic drugs for the treatment of overactive bladder (oxybutynin, tolterodine and darifenacin) on intracellular Ca(2+) mobilization in response to M(3) muscarinic receptor activation in bladder smooth muscle and submandibular gland cells isolated from Cynomolgus monkeys. Solifenacin concentration-dependently inhibited carbachol-induced Ca(2+) mobilization, with affinity constant values (pKi) of 8.5 +/- 0.053 in bladder smooth muscle cells and 8.2 +/- 0.051 in submandibular gland cells (n = 5). The pKi value of solifenacin was almost equivalent to the values of oxybutynin, tolterodine and darifenacin in bladder smooth muscle cells (8.7, 8.5 and 8.4, respectively), while being lower than those in submandibular gland cells (9.0, 8.7 and 8.8, respectively). The bladder-selectivity index (Ki ratio: submandibular gland/bladder) for solifenacin (2.1) was statistically higher, moreover, than those for oxybutynin, tolterodine and darifenacin (0.51, 0.65 and 0.46, respectively). These findings consequently indicate solifenacin's unique profile in terms of its selectivity for bladder smooth muscle cells over salivary gland cells in non-human primates, relative to oxybutynin, tolterodine and darifenacin. Solifenacin may, therefore, confer a promising therapeutic advantage for reducing adverse effects, such as dry mouth, exhibited by current antimuscarinic therapy for overactive bladder.

Animals↗
PubMed2006

Solifenacin succinate for the treatment of symptoms of overactive bladder.

BACKGROUND: Overactivity of the bladder detrusor muscle can result in urinary urgency, frequency, and incontinence. Antimuscarinic agents are the treatment of choice, as they reduce the contractility of this muscle. Solifenacin succinate (SOL) is a competitive muscarinic-receptor antagonist approved by the US Food and Drug Administration in late 2004 for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. OBJECTIVE: This article reviews the current primary literature concerning the pharmacokinetics, efficacy, and tolerability of SOL in the treatment of OAB. METHODS: Pertinent English-language articles were identified through a search of MEDLINE (1966-week 4, 2006), EMBASE (1991-first quarter of 2006), Current Contents/Clinical Medicine (week 10, 2005-week 9, 2006), the Cochrane Database of Systematic Reviews, MICROMEDEX Healthcare Series, and International Pharmaceutical Abstracts (1970-present). The search terms were overactive bladder, urinary incontinence, solifenacin, YM905, pharmacokinetics, and cost. RESULTS: SOL is highly lipophilic (50:1 octanol:water distribution at pH 7.0), completely orally bioavailable, and 98% protein bound. It is metabolized by the cytochrome P450 3A isozyme, and approximately 50% of a dose is eliminated renally as parent compound, with 1 active and 3 inactive metabolites. In two 12-week Phase III studies, patients receiving SOL 5 or 10 mg had significant reductions compared with placebo in the numbers of voids (P < or = 0.01), incontinence episodes (P < or = 0.05), and urgency episodes (P < or = 0.01) per 24 hours; the volume voided per micturition was significantly increased (P < or = 0.01). In a study that compared SOL 5 and 10 mg with tolterodine extended release 4 mg, both agents were associated with significant reductions in the number of voids per 24 hours (-2.45 and -2.24 episodes, respectively; P = 0.004 for noninferiority). In a study of pooled data from two 12-week studies, patients who received SOL 5 or 10 mg reported significant improvements in a number of quality-of-life domains (P < or = 0.05). In a pooled analysis of 4 studies, the most common adverse effects (occurring in > or =3% of any group) in patients receiving SOL 5 mg (n = 266) and 10 mg (n = 612) were dry mouth (10.9% and 27.1%, respectively), constipation (5.3% and 12.9%), and blurred vision (4.5% and 4.7%). CONCLUSIONS: In the studies reviewed, SOL was effective in the treatment of OAB with urge incontinence. Adverse effects included dry mouth, constipation, and blurred vision. Further studies are needed to determine the efficacy and tolerability of SOL in patients with hepatic or renal impairment.

Clinical Trials as Topic↗
PubMed2005

Recent developments in the management of overactive bladder: focus on the efficacy and tolerability of once daily solifenacin succinate 5 mg.

BACKGROUND: Overactive bladder (OAB) is a highly prevalent symptom complex that may be extremely distressing to the patient, and can be associated with co-morbidities and reduced quality of life (QoL). One of the major pathophysiological causes of OAB is overactivity of the detrusor muscle, mediated via muscarinic receptors in the bladder. Urgency is the defining symptom of OAB, yet a significant proportion of patients also suffer from incontinence, which is the most distressing symptom to the patient. As such, restoration of continence should be a primary treatment goal. However, effective treatments should also impact on the other key symptoms of OAB, such as micturition frequency and urgency. Non-pharmacologic interventions to treat OAB can be effective but require patients to be highly motivated. In terms of pharmacologic therapy, treatment with an antimuscarinic agent is the mainstay of current therapy. Solifenacin succinate is a once-daily oral antimuscarinic for the treatment of OAB. The recommended dose is 5mg once daily and can be increased to 10 mg once daily if 5 mg is well tolerated. OBJECTIVES: This paper reviews clinical experience with solifenacin 5 mg in patients with OAB as this is the recommended dose according to FDA product labeling. FINDINGS: In Phase 3 studies, based on data captured in 3-day micturition diaries, greater than half of patients who were incontinent at baseline no longer reported experiencing incontinence episodes after 12 weeks of double-blind treatment with solifenacin 5 mg. Furthermore, compared with placebo, solifenacin treatment resulted in statistically significant reductions in incontinence episodes, micturition frequency and urgency episodes, with significant increases in volume voided (based on an analysis of key symptom outcomes in two pooled Phase 3 studies presented here). The most common treatment-related adverse events were expected anticholinergic side effects (dry mouth, constipation, and blurred vision), and these were generally mild to moderate. Discontinuation rates due to adverse events in the treatment and placebo groups were comparable. CONCLUSION: Solifenacin 5 mg was found to be efficacious and had an acceptable tolerability profile in patients with OAB in these trials and this treatment may provide QoL benefits to patients.

Administration, Oral↗
PubMed2004

Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder.

PURPOSE: In this phase 3 trial we assessed the efficacy of solifenacin 5 mg and 10 mg daily in patients with symptoms related to overactive bladder. In addition, we assessed the safety and acceptability of solifenacin. MATERIALS AND METHODS: The study was a multicenter, multinational, randomized, double-blind, placebo controlled trial. Patients were randomized to 12-week once daily treatment with solifenacin 5 mg, solifenacin 10 mg or placebo. The primary efficacy variable was changed from baseline to study end point in mean number of micturitions per 24 hours. Secondary efficacy variables included changes from baseline in mean number of urgency, nocturia and incontinence episodes per 24 hours, and mean volume voided per micturition. RESULTS: Compared with changes obtained with placebo (-1.59), micturitions per 24 hours were statistically significantly decreased with solifenacin 5 mg (-2.37, p = 0.0018) and solifenacin 10 mg (-2.81, p = 0.0001). A statistically significant decrease was observed in the number of incontinence episodes with both solifenacin doses (5 mg, p = 0.002 and 10 mg, p = 0.016). This effect was also seen for episodes of urge incontinence (5 mg, p = 0.014 and 10 mg, p = 0.042). Of patients reporting incontinence at baseline, fully 50% achieved continence after treatment with solifenacin. Episodes of nocturia were statistically significantly decreased in patients treated with solifenacin 10 mg (-0.71, -38.5%) versus placebo (-0.52, -16.4%, p = 0.036). Episodes of urgency were statistically significantly reduced with solifenacin 5 mg (-2.84, -51%, p = 0.003) and solifenacin 10 mg (-2.90, -52%, p = 0.002). Mean volume voided per micturition was statistically significantly increased with both solifenacin doses (p = 0.0001). Treatment with solifenacin was well tolerated. Dry mouth, mostly mild in severity, was reported in 7.7% of patients receiving solifenacin 5 mg and 23% receiving solifenacin 10 mg (vs 2.3% with placebo). CONCLUSIONS: In this study treatment with solifenacin 5 mg and 10 mg once daily significantly improved all the major symptoms of overactive bladder including frequency, urgency and incontinence. Solifenacin 10 mg also decreased the frequency of nocturia. Solifenacin therapy was associated with a favorable tolerability profile and a low incidence of dry mouth, especially at the 5 mg starting dose.

Adolescent↗
PubMed2005

A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial.

OBJECTIVE: To compare two new generation antimuscarinics at their recommended doses for treatment of overactive bladder syndrome (OAB). METHODS: A prospective, double blind, double-dummy, two-arm, parallel-group, 12-week study was conducted to compare the efficacy and safety of solifenacin 5 or 10 mg and tolterodine extended release (ER) 4 mg once daily in OAB patients. After 4 weeks of treatment patients had the option to request a dose increase but were dummied throughout as approved product labelling only allowed an increase for those on solifenacin. RESULTS: Solifenacin, with a flexible dosing regimen, showed greater efficacy to tolterodine in decreasing urgency episodes, incontinence, urge incontinence and pad usage and increasing the volume voided per micturition. More solifenacin treated patients became continent and reported improvements in perception of bladder condition assessments. The majority of side effects were mild to moderate in nature, and discontinuations were comparable and low in both groups. CONCLUSIONS: Solifenacin, with a flexible dosing regimen, was found to be superior to tolterodine ER with respect to the majority of the efficacy variables.

Analysis of Variance↗
PubMed2006

Solifenacin significantly improves all symptoms of overactive bladder syndrome.

Overactive bladder syndrome (OAB) is a chronic condition characterised by urgency, with or without associated urge incontinence. Solifenacin succinate is a once daily, bladder selective antimuscarinic available in two doses (5 and 10 mg). The recommended dose is 5 mg once daily and can be increased to 10 mg once daily if 5 mg is well tolerated. This article presents pooled efficacy and safety data from four large, placebo-controlled, multinational phase III trials of solifenacin succinate with a total enrolment of over 2800 patients. Data from these trials show that solifenacin 5 and 10 mg once daily is significantly more effective than placebo at reducing urgency, incontinence, micturition frequency and nocturia and at increasing volume voided per micturition. Adverse events were mainly mild-to-moderate in all treatment groups. The results of these phase III trials support the use of solifenacin in the treatment of OAB.

Adolescent↗
PubMed2006

Multiple doses of the antimuscarinic agent solifenacin do not affect the pharmacodynamics or pharmacokinetics of warfarin or the steady-state pharmacokinetics of digoxin in healthy subjects.

AIMS: Solifenacin succinate is used for the treatment of overactive bladder (OAB). The potential for pharmacokinetic and/or pharmacodynamic interactions between solifenacin and warfarin or digoxin was investigated. METHODS: The solifenacin-warfarin study was a two-period crossover trial conducted in healthy males. Subjects received warfarin on the 10th day of 16 days of dosing with either solifenacin or placebo. The solifenacin-digoxin study was an one-sequence crossover trial conducted in healthy males and females. Following a phase-in period for digoxin, solifenacin was administered concomitantly with the drug on days 9-18. RESULTS: The AUC(PT; 0-168 h) following a single dose of warfarin was unchanged in the presence of solifenacin [point estimate = 1.005; 90% confidence interval (CI) 0.98, 1.02)]. The AUC(0-infinity) values for both warfarin enantiomers were also unchanged. A small increase in the C(max) of digoxin was observed during treatment with solifenacin, but for AUC(ss,tau) and C(max) the 90% CI fell within the prespecified interval of 0.80-1.25. Combined administration of solifenacin and warfarin or digoxin was well tolerated. CONCLUSIONS: Since the pharmacokinetics and pharmacodynamics of a single dose of warfarin and the steady-state pharmacokinetics of digoxin were not affected by coadministration of solifenacin in healthy subjects, the need for dosing adjustments for digoxin and/or warfarin does not seem warranted.

Administration, Oral↗
PubMed2005

Solifenacin: as effective in mixed urinary incontinence as in urge urinary incontinence.

Patients with mixed urinary incontinence (MUI) are frequently treated with antimuscarinic therapy, despite little data being previously published for this patient group. We present a subgroup analysis of patients with overactive bladder syndrome, assessing the efficacy of once-daily solifenacin succinate in patients with MUI (n = 1041) or urge urinary incontinence (UUI; n = 1648) only. A greater proportion of patients receiving solifenacin achieved resolution of incontinence in both the MUI and UUI groups (MUI: 5 mg = 43%, 10 mg = 49%; UUI: 5 mg = 55%, 10 mg = 54%) compared with patients receiving placebo (MUI 33%, UUI 35%). Baseline to endpoint improvements in all other symptoms were statistically significant vs placebo for both solifenacin doses in both cohorts. The incidence of adverse events was comparable between the MUI and UUI cohorts. This analysis shows that once-daily solifenacin was as effective and well tolerated in patients with MUI as in patients with UUI.

Aged↗
PubMed2006

Pharmacokinetic effect of ketoconazole on solifenacin in healthy volunteers.

Solifenacin succinate (YM905) is a new, once-daily, orally administered muscarinic receptor antagonist designed to treat overactive bladder. The metabolism of solifenacin involves hepatic cytochrome P450 (CYP) 3A4; therefore, the pharmacokinetics of solifenacin may be affected by drugs that inhibit CYP3A4. This study aimed to examine the effects of co-administration of ketoconazole, a potent CYP3A4 inhibitor, on the pharmacokinetics of solifenacin in healthy volunteers. In a single-site, open-label, monosequence, crossover study, 17 healthy men and women aged 18 to 65 years received a single 10 mg oral dose of solifenacin, which is is the highest available dose. After a 14-day wash-out period, they began 20 days of oral ketoconazole at a dose of 200 mg once daily. A single 10 mg dose of solifenacin was administered again on day 7 of ketoconazole treatment. Pharmacokinetics was assessed using the standard measurements of maximum plasma concentration (Cmax), time to Cmax, area under the curve (AUC), and elimination half-life (t1/2). Co-administration of ketoconazole resulted in a 1.43 times increase in the C(max) of solifenacin and an approximately 2 times increase in AUC. The mean t1/2 of solifenacin was extended from 49.3 to 77.5 hr whereas time to Cmax did not change. No substantial increase in the overall rate of adverse events, and no significant effects on vital signs, electrocardiography, clinical laboratory values, or physical examinations were noted. Administration of 200 mg ketoconazole once daily in healthy male volunteers resulted in a 2 times increase in exposure of a single 10 mg dose of solifenacin. Since ketoconazole is one of the strongest inhibitors of CYP3A4, it is expected that co-administration of other CYP3A4 inhibitors will not result in a stronger increase in solifenacin exposure.

Adolescent↗