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At least 1,513 records · Page 84Linked to original sources
PubMed2005

Transdermal oxybutynin in the treatment of adults with overactive bladder: combined results of two randomized clinical trials.

The safety and efficacy of oxybutynin transdermal delivery system (oxybutynin-TDS) versus placebo in adults with urge and mixed urinary incontinence was investigated using combined results from double-blind stages of 2 phase 3 clinical trials. Study 1: placebo-controlled, parallel-group comparison of 3 oxybutynin-TDS doses in 12-week double-blind and open-label periods, followed by a 28-week open-label extension. Study 2 was a 12-week randomized, double-blind, placebo-controlled comparison of oxybutynin-TDS versus long-acting tolterodine and placebo, followed by a 52-week open-label extension. Efficacy analysis included 241 patients receiving oxybutynin-TDS, 244 receiving placebo. Most participants were Caucasian women (92%). Approximately 60% received prior anticholinergic therapy. Primary outcome was determined by changes from baseline to end of treatment in frequency of incontinence episodes, frequency of urination, and void volume. Oxybutynin-TDS was significantly more effective than placebo in reducing median daily incontinence episodes (-3.0 vs placebo -2.0; P=.00004) and daily urinary frequency (-2.0 vs -1.0; P=.0023), and in increasing void volume (25 mL vs 5.5 mL; P<.00001). Overall rates of anticholinergic adverse events (AEs) were 12.8% for oxybutynin-TDS and 11.0% for placebo (P=0.5421). The most common systemic anticholinergic AEs were dry mouth (7.0% for oxybutynin-TDS vs 5.3% for placebo) and constipation (2.1% vs 2.0%). Application site erythema occurred in 7.0% of participants who received oxybutynin-TDS (3.7% discontinuation rate); pruritus occurred in 16.1% (3.3% discontinuation rate). Transdermal oxybutynin was shown to be efficacious, with a proven safety profile. It may be utilized for patients with overactive bladder as a treatment option that could enhance compliance.

Administration, Cutaneous↗
PubMed2005

Efficacy and tolerability of darifenacin, a muscarinic M3 selective receptor antagonist (M3 SRA), compared with oxybutynin in the treatment of patients with overactive bladder.

A randomized, double-blind, placebo-controlled, four-way crossover, safety study of darifenacin versus oxybutynin was carried out on 76 patients with overactive bladder (OAB). Adults with OAB received 2 weeks each of darifenacin 15 and 30 mg once daily (q.d.), oxybutynin 5 mg three times daily (t.i.d.) and placebo, in random sequence at 10-day intervals. Darifenacin and oxybutynin significantly reduced incontinence episodes, and the number/severity of urgency episodes (all P<0.05 versus placebo). Improvements in OAB symptoms with darifenacin were dose-dependent. Dry mouth was less common with darifenacin 15 mg than oxybutynin (13% and 36%; P<0.05), while constipation was comparable (10% and 8%, respectively). Corresponding rates for darifenacin 30 mg were 34% and 21%, respectively. Patients only reported blurred vision or dizziness with oxybutynin (3% and 2%, respectively). Darifenacin (15 mg q.d.) provides comparable efficacy with improved tolerability versus oxybutynin (5 mg t.i.d.) in the treatment of patients with OAB.

Adolescent↗
PubMed2001

Comparison of the inhibitory effects of cromakalim and pinacidil (potassium channel openers) with those of oxybutynin on stimulated guinea pig and rabbit detrusor muscle strips.

To compare the inhibitory effects of a new group of smooth muscle relaxants, the potassium channel openers cromakalim and pinacidil, with those of oxybutynin on detrusor muscle stimulation in animals. Detrusor strips of guinea pigs (n=16) and rabbits (n=20) were mounted in organ bath for recording of isometric tension. Alpha,beta-methylene ATP (10(-7), 10(-6), 10(-5) M), carbachol (10(-6), 10(-5), 3 x 10(-5), 5 x 10(-5) M) and transmural electrical-field stimulation (TES) were applied and concentration-response curves in the absence or presence of cromakalim (10(-6), 10(-5) M), pinacidil (10(-5), 5 x 10(-5) M) and oxybutynin (10(-5), 5 x 10(-5) M) were generated. All curves were displaced to the right in a concentration-dependent manner. The order of potency of inhibition was as follows: alpha,beta-methylene ATP (pinacidil>oxybutynin>cromakalim in guinea pigs; pinacidil>cromakalim>oxybutynin in rabbits); TES (pinacidil>cromakalim>oxybutynin in guinea pigs; cromakalim>oxybutynin>pinacidil in rabbits); carbachol (oxybutynin>pinacidil>cromakalim in guinea pigs; oxybutynin>cromakalim>pinacidil in rabbits). Cromakalim and pinacidil mainly inhibited purinergic-induced (alpha,beta-methylene ATP and TES) detrusor contractions.

Animals↗
PubMed2001

Combined pharmacotherapy for nocturnal enuresis.

Nocturnal enuresis is a common childhood disorder. Tricyclic antidepressants and anticholinergic agents have been the well accepted pharmacological treatment for this disorder and are efficacious in 40-70% and 10-50% of cases, respectively. The present study was performed to evaluate the effect of a combined treatment of tricyclic antidepressant and an anticholinergic agent. Twenty-two children aged 6-12 years with primary monosymptomatic nocturnal enuresis who did not prefer to use a conditioning alarm were given a combined treatment of these drugs. After a control period of 1 month, each patient was treated for 6 months and then observed for 3 months. A 30-mg dose of amitriptyline or imipramine was given with either 2-4 mg oxybutinin or 10-20 mg propiverine. Efficacy was determined relative to the number of wet nights per week compared with the control period, with more than a 50% decrease in wet nights per week taken to indicate efficacy. The mean wet nights per week decreased from 6.1 to 1.7 (P<0.01), and efficacy was established in 20 patients (90.9%). Relapses occurred in 60.0% of patients during the follow-up period. No significant side effects were observed. The efficacy of the combined therapy in monosymptomatic nocturnal enuresis appears to be greater than that reported for either drug alone, and therefore can be a choice of treatment in order to motivate children with nocturnal enuresis.

Amitriptyline↗
PubMed2005

A polymeric nanoparticle consisting of mPEG-PLA-Toco and PLMA-COONa as a drug carrier: improvements in cellular uptake and biodistribution.

PURPOSE: To evaluate a new polymeric nanoparticulate drug delivery formulation that consists of two components: i) an amphiphilic diblock copolymer having tocopherol moiety at the end of the hydrophobic block in which the hydrophobic tocopherol moiety increases stability of hydrophobic core of the nanoparticle in aqueous medium; and ii) a biodegradable copolyester having carboxylate end group that is capable of forming ionic complex with positively charged compounds such as doxorubicin. METHODS: A doxourubicin-loaded polymeric nanoparticle (Dox-PNP) was prepared by solvent evaporation method. The entrapment efficiency, size distribution, and in vitro release profile at various pH conditions were characterized. In vitro cellular uptake was investigated by confocal microscopy, flow cytometry, and MTT assay using drug-sensitive and drug-resistant cell lines. Pharmacokinetics and biodistribution were evaluated in rats and tumor-bearing mice. RESULTS: Doxorubicin (Dox) was efficiently loaded into the PNP (higher than 95% of entrapment efficiency), and the diameter of Dox-PNP was in the range 20-25 nm with a narrow size distribution. In Vitro study showed that Dox-PNP exhibited higher cellular uptake into both human breast cancer cell (MCF-7) and human uterine cancer cell (MES-SA) than free doxorubicin solution (Free-Dox), especially into drug-resistant cells (MCF-7/ADR and MES-SA/Dx-5). In pharmacokinetics and tissue distribution study, the bioavailability of Dox-PNP calculated from the area under the blood concentration-time curve (AUC) was 69.8 times higher than that of Free-Dox in rats, and Dox-PNP exhibited 2 times higher bioavailability in tumor tissue of tumor-bearing mice. CONCLUSIONS: Dox-PNP exhibited enhanced cellular uptake of the drug. In the cytotoxic activity study, this improved cellular uptake was proved to be more advantageous in drug-resistant cell. Dox-PNP exhibited much higher bioavailability in blood plasma and more drug accumulation in tumor tissue than conventional doxorubicin formulation. The results of this study suggest that the PNP system is an advantageous carrier for drug delivery.

Animals↗
PubMed2005

Comparison of dry mouth in women treated with extended-release formulations of oxybutynin or tolterodine for overactive bladder.

The incidence, severity and tolerability of dry mouth was compared in 790 women with overactive bladder who were treated with extended-release oxybutynin chloride 10 mg/day or extended-release tolterodine tartrate 4 mg/day for 12 weeks in a multicenter, double-blind, parallel-group study. Dry mouth was the most common adverse event associated with treatment, with an incidence rate of 28.1% in the oxybutynin group and 21.6% in the tolterodine group (P = 0.039). The majority of dry mouth events were mild in both treatment groups. Severe dry mouth occurred in 1.5% and 0.5% of patients in the oxybutynin and tolterodine groups, respectively (P = 0.173). Seven patients on extended-release oxybutynin and 4 patients on extended-release tolterodine discontinued treatment due to dry mouth (P = 0.380). The results of this analysis showed that dry mouth was common with both treatments, but most events were mild; there was no difference in the rate of severe dry mouth or in the rate of withdrawal due to dry mouth.

Adolescent↗
PubMed2002

Pharmacologic treatment for detrusor overactivity.

Recent pharmacologic treatment for detrusor overactivity has resulted in more favorable side effect profiles, not only because of the use of different drug delivery systems for older drugs but perhaps also due to the improved bladder selectivity of newer antimuscarinic agents. These developments translate into higher patient compliance and better long-term results with the newer agents over generic immediate-release oxybutynin for the treatment of the overactive bladder.

Benzhydryl Compounds↗
PubMed2002

Advances in drug delivery: improved bioavailability and drug effect.

Alterations in drug delivery produce substantial changes in the bioavailability of anticholinergic agents. These bioavailability differences change the efficacy and tolerability of this drug class, which consistently enhances patient compliance and overall drug effect. In order for drug delivery to alter successfully the bioavailability of a specific agent, the metabolism of that agent and the effect of the degradatory pathway on drug-parent compound levels need to be established. This will enable researchers to design improved or altered delivery pathways to maximize the benefits of these agents. Intestinal metabolism is known to affect certain agents, specifically oxybutynin chloride. Therefore, delivery techniques have been designed that either substantially lower or totally bypass intestinal (presystemic) metabolism. These alternate paths include extended-release oral, cutaneous, intravesical, and intravaginal routes. In addition, improvements in drug delivery have also been found to influence positively efficacy and tolerability profiles associated with tolterodine tartrate, another anticholinergic agent. A long-acting oral formulation has been shown to increase drug efficacy while decreasing tolerability concerns and side effects such as xerostomia. These salubrious effects are, in part, due to the more stable serum-drug concentrations that are imparted by this long-acting formulation.

Biological Availability↗
PubMed2003

Update on overactive bladder: pharmacologic approaches on the horizon.

Limitations exist with regard to the array of available agents for the pharmacologic therapy of overactive bladder, including issues of efficacy and tolerability. It is clear that the ideal agent for this condition has not been identified. However, several new pharmacologic treatments, including some with novel approaches to drug delivery, have emerged in clinical development over the past few years. These agents include a variety of anticholinergics and others. In initial studies, some of the agents appear to compare favorably with existing therapies. Whether these promising results will hold up when subjected to large-scale, well-controlled clinical trials is unclear.

Administration, Cutaneous↗
PubMed2003

Muscarinic receptors: what we know.

An understanding of muscarinic receptors is tantamount to an understanding of overactive bladder. The M(3) muscarinic receptor subtype is responsible for detrusor smooth muscle contraction and it exerts an exocrine function in the salivary glands. Alterations in the receptor's response to acetylcholine as a result of injury may lead to hypersensitivity and overactivity. The M(2) receptor subtype, which is mainly responsible for cardiac function, is the muscarinic receptor of highest proportion in the detrusor. M(2) also may play a role in detrusor contraction in injury and pathologic states. Muscarinic antagonists are the mainstay of pharmacotherapy for overactive bladder, but those that are available are not tissue specific. Growing knowledge of the nuances of receptor-ligand behavior and interaction between muscarinic receptors subtypes may provide novel targets for future drug development, improve efficacy, and reduce bothersome side effects.

Animals↗
PubMed2003

Overactive bladder: improving the efficacy of anticholinergics by dose escalation.

Overactive bladder (OAB) affects millions of people in the United States and significantly impacts their quality of life. New antimuscarinic anticholinergic medications have improved the treatment of OAB, offering patients efficacy equal to that of immediate-release oxybutynin with fewer side effects and an improved dosing schedule. The commonly reported range of reduction of urge incontinence episodes is between 46% and 92%. Although patients are improving, continence rates are lower and many responders continue to leak significantly. The literature supports that the efficacy of anticholinergics is enhanced by dose escalation, but using higher dosages has not become routine in clinical practice. Although dose escalation can be implemented with all of the anticholinergics, it is done most easily and approved by the US Food and Drug Administration with extended-release oxybutynin. This paper critically evaluates the pros and cons of dose escalation in the hope to improve efficacy in patients with OAB.

Benzhydryl Compounds↗
PubMed2005

Intravesical therapy for overactive bladder.

Overactive bladder and urgency incontinence are common conditions generally treated with oral anticholinergic therapy. Despite the development of new antimuscarinic agents, many patients do not tolerate or fail to respond to oral therapy. Intravesical instillation therapy can provide an alternative method of managing bladder overactivity. Intravesical instillation of anticholinergics such as oxybutynin and atropine can achieve cholinergic blockade without producing systemic side effects. Botulinum A toxin injected directly into the detrusor has been shown in preliminary studies to increase bladder capacity and decrease uncontrolled bladder contractility for up to 6 months. Intravesical local anesthetics such as lidocaine and bupivacaine block the conduction of unmyelinated C fibers and when administered into the bladder, lead to an increase in functional bladder capacity. Intravesical capsaicin and resiniferatoxin also affect afferent innervation by blocking C-fiber afferents, leading to decreased bladder contractility and increased bladder capacity. Intravesical instillation therapy can provide an alternative treatment for the management of overactive bladder.

Administration, Intravesical↗