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Rodney A Appell

Publications and source records attributed to Rodney A Appell.

34 records · Page 2Linked to original sources
PubMed2004

Effect of antacid on the pharmacokinetics of extended-release formulations of tolterodine and oxybutynin.

BACKGROUND: In general, extended-release (ER) formulations are designed to prolong the duration of efficacy and reduce the adverse effects of a drug. These formulations often contain the entire daily dose in a single tablet. Therefore, failure of the ER mechanism not only diminishes the desired benefits, but may temporarily expose the patient to drug concentrations higher than those released from a conventional tablet. In this study we determined whether pH has an effect on drug release from the ER formulations of oxybutynin (OROS technology) and tolterodine (membrane coated beads) in vitro and in vivo. STUDY DESIGN: In vitro studies were based on standardised dissolution experiments for each drug in media of different pH (artificial gastric fluid at pH 1.2, artificial intestinal fluid at pH 7.5, and water). In the two separate, identically designed in vivo studies, single doses of each drug were administered alone and with an antacid to male and female healthy volunteers aged 18-45 years. The randomised, crossover, open-label in vivo studies employed a validated assay to determine plasma concentrations of tolterodine and its metabolite 5-hydroxymethyl tolterodine (5-HM), or oxybutynin and its metabolite N-desethyloxybutynin. RESULTS: The in vitro study showed similar slow and steady drug release from ER-oxybutynin in each pH medium, with 64-71% released after 12 hours. Drug release from ER-tolterodine was steady and slow in artificial gastric fluid, with 72.5% of drug released after 12 hours. However, drug release was much faster in artificial intestinal fluid and water, where 69.8% and 69.1%, respectively, of the drug was released within 4 hours. These in vitro results were consistent with the findings of the in vivo studies. In vivo, the pharmacokinetic profile (peak plasma concentration [C(max)] and area under the concentration-time curve) of ER-oxybutynin was similar after administration with or without antacid, whereas C(max) values of both tolterodine and 5-HM increased significantly when ER-tolterodine was administered with antacid (p < or = 0.017 vs ER-tolterodine alone). CONCLUSIONS: Changes in pH affected the release of tolterodine from ER-tolterodine, while they had no effect on the release of oxybutynin from the proprietary ER technology used in ER-oxybutynin. The technology employed in ER formulations thus determines sensitivity of drug release to external factors.

Adolescent↗
PubMed2003

Baseline abdominal pressure and valsalva leak point pressures-correlation with clinical and urodynamic data.

AIMS: To characterize the factors contributing to changes in baseline abdominal pressure (P(abd)) and the correlation between DeltaVLPP, VLPP(tot), and other clinical and urodynamic variables. METHODS: Two hundred sixty-four female patients who had undergone an anti-incontinence procedure between February 1994 and October 1999 were retrospectively reviewed. The urodynamics performed for each patient included abdominal and vesical pressures measured in a standardized manner with the patient sitting upright and the pressure sensors maintained at the level of the symphysis pubis. VLPP was determined at bladder volumes of 200 mL during a gradually increasing Valsalva maneuver. RESULTS: Baseline P(abd) varied between 10 and 55 cm H(2)O (mean, 32.7 +/- 8.8) and were significantly correlated with patient weight (P<0.001) and with patient body mass index (P<0.001). Baseline P(abd) was not found to be correlated with patient age, Baden and Walker Classification of the grading of pelvic floor prolapse, degree of incontinence (determined by the number of pads used per day), or prior surgical procedures for stress incontinence. Higher baseline P(abd) were significantly correlated with the peak abdominal pressure reached during the Valsalva maneuver (P<0.0001) and with VLPP(tot) (P<0.0001) but not with DeltaVLPP. Higher VLPP(tot) significantly correlated with decreased age (P=0.004), less severe incontinence (P=0.004), higher peak Valsalva pressure (P<0.0001), and the ability to increase abdominal pressure for a longer period of time (time to peak P(abd) during Valsalva). VLPP(tot) and DeltaVLPP had similar statistical correlation with all the clinical variables examined and neither could predict the outcome of any anti-incontinence surgery. By using a VLPP of 60 cm H(2)O as a cutoff to differentiate severe ISD from GSUI, 211 (67.4%) of the patients would be categorized as having ISD according to their DeltaVLPP compared with only 106 (40.1%) by using the VLPP(tot). CONCLUSIONS: Baseline P(abd) varies considerably among patients, is correlated with patient weight and habitus. In addition, it varies with both the ability to be increased for longer periods of time and with VLPP(tot). Looking at VLPP(tot) and DeltaVLPP will result in a different categorization of the type of incontinence in at least 25% of patients and, thus, affect the physician's selection of an anti-incontinence procedure for an individual patient.

Abdomen↗
PubMed2003

Functional brain imaging and the bladder: new insights into cerebral control over micturition.

Mechanisms for cerebral control over the micturition process remain poorly elucidated. The knowledge is based largely on human pathophysiology and data derived from electrophysiologic testing in animals. Recent advances in dynamic functional brain imaging technologies including positron-emission tomography, single photon emission computed tomography, and functional magnetic resonance imaging have allowed new insights into how the human brain regulates this process. This article discusses animal studies, which provided the foundation for our understanding of cerebral control over micturition, and recent human studies, implementing functional brain imaging to enhance our knowledge of this complex phenomenon.

Animals↗
PubMed2003

Advancements in minimally invasive treatments for female stress urinary incontinence: radiofrequency and bulking agents.

Continuous advancements in materials technology have provided the possibility that multiple new urethral bulking agents will be available soon. Experience continues to accrue in clinical trials for urethral bulking with these agents. Parallel use for the indication of pediatric vesicourethral reflux also has provided evidence of biologic activity related to these compounds. All of the agents closest to complete analysis are synthetic and represent a variety of material types and characteristics. As these materials evolve, understanding of the preferential injection technique is being gained. Delivery methods and sites may prove to alter the biologic activity of these compounds substantially. Emphasis on other minimally invasive options for the surgical treatment of stress incontinence also has resulted in the development of radiofrequency vesicourethral suspension. Improved understanding of thermal application to tissue, acute and chronic tissue response to this application, and accumulating human experience with this method of therapy has provided an acceptable tolerability profile for this therapy. This profile may provide application of this method of therapy to an in-office treatment setting, precluding hospitalization and substantially decreasing convalescence times.

Administration, Intravaginal↗
PubMed2003

Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial.

OBJECTIVE: To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder. PATIENTS AND METHODS: The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18,2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated. RESULTS: Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n = 391) or tolterodine (n = 399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency (P = .003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine (P = .03). Dry mouth, usually mild, was more common with oxybutynin (P = .02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events. CONCLUSIONS: Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system.

Administration, Oral↗
PubMed2003

Pharmacokinetics, metabolism, and saliva output during transdermal and extended-release oral oxybutynin administration in healthy subjects.

OBJECTIVE: To compare the pharmacokinetics and adverse effect dynamics of 2 modified-release oxybutynin treatments. SUBJECTS AND METHODS: Between October 15 and November 6, 2001, 13 healthy subjects (7 men and 6 women) participated in a randomized, 2-way crossover study of transdermal (Oxytrol, 3.9 mg/d) and extended-release oral (Ditropan XL, 10 mg) oxybutynin. Multiple blood and saliva samples were collected. Pharmacokinetic parameters and total salivary output were assessed. Statistical analyses included 95% confidence intervals, paired t test, analysis of variance, and linear regression. RESULTS: Steady-state plasma concentrations were achieved after the first transdermal application and after the second extended-release oral dose. Mean +/- SD 24-hour oxybutynin areas under the concentration-time curve were comparable during transdermal and oral extended-release treatments, 10.8 +/- 24 vs 9.2 +/- 33 ng x h(-1) x mL(-1), respectively. However, the ratio of area under the curve (N-desethyloxybutynin/oxybutynin) after transdermal administration (1.2 +/- 03) was significantly lower (P < .001) than after extended-release oral administration (4.1 +/- 0.9). Mean plasma concentrations were less variable during transdermal compared with extended-release oral administration. Mean +/- SD saliva output was greater during transdermal than extended-release oral treatment (15.7 +/- 93 vs 12.2 +/- 6.8 g, respectively; P = .02). Lower N-desethyloxybutynin during transdermal application was associated with greater saliva output (r = -059, P = .04). No clinically important treatment-related adverse effects were observed. CONCLUSIONS: Transdermal oxybutynin administration results in greater systemic availability and minimizes metabolism to N-desethyloxybutynin compared with extended-release oral administration. Lower N-desethyloxybutynin plasma concentration and greater saliva output during transdermal treatment correspond to the reported low incidence of dry mouth in patients with overactive bladder.

Administration, Cutaneous↗
PubMed2003

Overactive bladder in special patient populations.

It is now well accepted that overactive bladder (OAB) negatively affects the quality of life of a large number of persons and that the primary mode of therapy is the use of medication-currently antimuscarinic agents. However, it is also important for physicians to understand how the use of these drugs affects specific groups of patients. Most of the concern in this area focuses on the potential for these populations to experience certain adverse events or side effects from the use of antimuscarinic agents; this has prevented these drugs from being prescribed in these populations to the same degree as in the general population of OAB sufferers. The purpose of this article is to review these specific populations of OAB patients, including pediatric, geriatric, and pregnant patients, men with prostate problems, and patients in whom OAB is of neurogenic origin, and to discuss what is currently known about the use of antimuscarinic agents in these groups.

Journal Article↗
PubMed2002

De novo urge syndrome and detrusor instability after anti-incontinence surgery: current concepts, evaluation, and treatment.

The onset of de novo irritative voiding symptoms after anti-incontinence surgery for stress urinary incontinence is troubling to both patient and physician alike. At present, mechanisms responsible for the development of these symptoms are incompletely elucidated. Although bladder outlet obstruction may certainly be a cause, correct diagnosis and treatment of this condition in its more insidious manifestation may be difficult. In addition, alternative etiologic factors related to surgical technique during outlet enhancing surgery may play a role, prompting a rethinking of these procedures. In this discussion, we review changes in voiding physiology and mechanisms for voiding dysfunction after anti-incontinence surgery, emphasizing de novo urge syndrome and detrusor instability. In addition, we present our approach to the evaluation, diagnosis, and treatment of these challenging patients.

Humans↗
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

Impaired detrusor contractility: anything new?

Impaired detrusor contractility (IDC) is a poorly defined entity that represents a treatment challenge for the urologist. The etiology of IDC is variable and may include neurologic disorders, inflammatory conditions, and pharmacologic and psychogenic causes. The gold standard for the treatment of IDC is clean intermittent catheterization (CIC). Although well-established as efficacious and safe, CIC may be conceived as a major burden on a patient's quality of life and has been associated with urinary tract infections and urethral and/or bladder injury. Alternative treatment modalities for IDC can be divided into interventions at the nervous system supplying the bladder, the bladder itself, or the bladder outlet. We review and discuss novel and creative treatment options for patients with IDC that have been developed or tested over the past decade.

Humans↗
PubMed2002

Surgical management of overactive bladder.

The majority of patients with overactive bladder (OAB) can be managed with office-based techniques. When medical therapy fails as treatment for OAB, surgical intervention ranging from electric stimulation administered in the office to extensive procedures, such as augmentation or urinary diversion, may be needed. Any surgical intervention should be tailored to the patient with consideration of the degree of his or her discomfort, underlying pathology, general health, and obviously, the patient's own motivation.

Electric Stimulation Therapy↗
PubMed2002

Beyond collagen: injectable therapies for the treatment of female stress urinary incontinence in the new millennium.

Previous experience with GAX-collagen has shown that the endoscopic correction of female SUI is both possible and effective. It is clear, however, that durability remains a primary concern when implementing this approach to treatment. The availability of recently developed and newly emerging materials, carefully designed using the tenets and techniques of biotechnology and materials science, may provide solutions to some of the difficulties beleaguering this treatment option. Results with currently available injectables are summarized in Table 1. Careful review and critical analysis of new bulking agents will soon reveal which materials approach the therapeutic ideal. It is likely that the ultimate choice of a particular substance, synthetic or biologic, may best be determined by the clinical circumstances involving the individual patient.

Biocompatible Materials↗
PubMed2002

The newer antimuscarinic drugs: bladder control with less dry mouth.

Two newer antimuscarinic anticholinergic drugs--tolterodine and extended-release oxybutynin--are approximately as effective in treating overactive bladder as immediate-release oxybutynin, but are more tolerable. I review clinical trial data on the newer agents.

Benzhydryl Compounds↗
PubMed2002

Selecting a medical therapy for overactive bladder.

Immediate-release oxybutynin was the gold standard for pharmacologic treatment of overactive bladder for nearly 30 years. Intolerable systemic side effects, in particular dry mouth, limited its clinical utility, resulting in poor patient compliance with dosing regimens. Multiple studies have demonstrated the vastly superior tolerability of tolterodine, extended-release tolterodine, and extended-release oxybutynin over that of immediate-release oxybutynin at equivalent doses, and in the case of extended-release oxybutynin even to twice the dose of the original immediate-release form. With different drug delivery systems and, perhaps, with better bladder selectivity, these new oral agents have favorable side effect profiles, which translate into higher patient compliance and fewer treatment withdrawals or dosage reductions.

Journal Article↗