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1.
J Pediatr Urol ; 20(4): 603.e1-603.e8, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38871547

RESUMEN

INTRODUCTION AND OBJECTIVE: Desmopressin is well accepted as first-line medical therapy for enuresis. If ineffective, combination therapy of desmopressin + oxybutynin or desmopressin + imipramine has been used. This study assessed the efficacy of adjunct therapy with either imipramine or oxybutynin in the management of enuresis patients who failed desmopressin treatment. STUDY DESIGN: A retrospective chart review of our database for patients with enuresis was performed. Patients who were prescribed desmopressin, oxybutynin, and imipramine over 14 years for enuresis were included. Two cohorts of patients were examined; group OXY was treated with desmopressin and oxybutynin, and group IMP received desmopressin and imipramine. Pretreatment measurement of Vancouver Symptom Scores (VSS) were used to compare groups using the VSS question "I wet my bed at night" where 4: every night, 3: 4-5 nights per week, 2: 1-2 nights per week, 1: 3-4 nights per month, and 0: never. International Children's Continence Society (ICCS) criteria for continence success was utilized to determine outcomes. RESULTS: 2521 patients prescribed one of the 3 medications were identified. Among them, 81 patients (mean age: 10.5 ± 2.8 years) received combination therapy. Of which, 55 were male and 26 female. Specifically, 58 were prescribed both desmopressin and imipramine (group IMP), 23 desmopressin and oxybutynin (group OXY), and 4 transitioned from OXY to IMP. Mean pretreatment VSS showed no difference between groups. Both groups experienced minimal drops in wet nights with desmopressin alone. A comparison revealed that group IMP reduced wet nights significantly more than group OXY (VSS wet night score 0.7 ± 1.2 vs. 2.3 ± 1.1 respectively, p < 0.0001). Non-intent-to-treat complete response rate was 68% vs 5% (OR = 42.5, p < 0.001) (IMP vs. OXY respectively). Intent-to-treat response rates were 58%. DISCUSSION: Although first-line desmopressin treatment for enuresis is effective, it does not work for all patients, and many parents and children desire nighttime dryness. Clinicians have combined desmopressin with oxybutynin or imipramine for improved results, but research comparing these modalities is scarce. Our study suggests that the desmopressin and imipramine combination is superior at reducing nights wet compared to desmopressin and oxybutynin, attributed to imipramine's probable central mechanism rather than its secondary anticholinergic properties. Limitations include a modest sample size, retrospective design, and subjective responses to the Vancouver questionnaire. CONCLUSION: A combination of desmopressin and imipramine was more effective in reducing wet nights and had a complete response rate that was 42.5 times greater than desmopressin and oxybutynin.


Asunto(s)
Fármacos Antidiuréticos , Desamino Arginina Vasopresina , Quimioterapia Combinada , Imipramina , Ácidos Mandélicos , Enuresis Nocturna , Humanos , Ácidos Mandélicos/administración & dosificación , Ácidos Mandélicos/uso terapéutico , Desamino Arginina Vasopresina/administración & dosificación , Desamino Arginina Vasopresina/uso terapéutico , Estudios Retrospectivos , Niño , Masculino , Femenino , Imipramina/administración & dosificación , Imipramina/uso terapéutico , Enuresis Nocturna/tratamiento farmacológico , Fármacos Antidiuréticos/administración & dosificación , Fármacos Antidiuréticos/uso terapéutico , Adolescente , Resultado del Tratamiento
2.
J Phys Chem B ; 128(26): 6327-6337, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38913878

RESUMEN

Transdermal behavior is a critical aspect of studying delivery systems and evaluating the efficacy of cosmetics. However, existing methods face challenges such as lengthy experiments, high cost, and limited model accuracy. Therefore, developing accurate transdermal models is essential for formulation development and effectiveness assessment. In this study, we developed a multiscale model to describe the transdermal behavior of active ingredients in the stratum corneum. Molecular dynamics simulations were used to construct lipid bilayers and determine the diffusion coefficients of active ingredients in different regions of these bilayers. These diffusion coefficients were integrated into a multilayer lipid pathway model using finite element simulations. The simulation results were in close agreement with our experimental results for three active ingredients (mandelic acid (MAN), nicotinamide (NIC), and pyruvic acid (PYR)), demonstrating the effectiveness of our multiscale model. This research provides valuable insights for advancing transdermal delivery methods.


Asunto(s)
Administración Cutánea , Membrana Dobles de Lípidos , Simulación de Dinámica Molecular , Niacinamida , Ácido Pirúvico , Niacinamida/química , Niacinamida/administración & dosificación , Membrana Dobles de Lípidos/química , Ácido Pirúvico/química , Ácidos Mandélicos/química , Ácidos Mandélicos/administración & dosificación , Difusión , Piel/metabolismo , Piel/química
3.
Urologie ; 63(7): 693-701, 2024 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-38755461

RESUMEN

Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is a need for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6 years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38 patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94 cm H2O ± 26.12 standard deviation (SD) to 21.07 cm H2O ± 17.32 SD (P < 0.001, n = 34). Maximum bladder pressure (MBC) increased by 34% from 260.45 ml ± 200.26 SD to 348.45 ml ± 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be a useful alternative for patients who do not respond to other therapies or suffered side effects.


Asunto(s)
Ácidos Mandélicos , Vejiga Urinaria Neurogénica , Vejiga Urinaria Hiperactiva , Humanos , Administración Intravesical , Alemania , Ácidos Mandélicos/uso terapéutico , Ácidos Mandélicos/administración & dosificación , Ácidos Mandélicos/efectos adversos , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/uso terapéutico , Antagonistas Muscarínicos/efectos adversos , Resultado del Tratamiento , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Agentes Urológicos/uso terapéutico , Agentes Urológicos/administración & dosificación , Agentes Urológicos/efectos adversos
4.
Eur Urol Focus ; 10(2): 325-331, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38402104

RESUMEN

BACKGROUND AND OBJECTIVE: There is a reported association between overactive bladder (OAB) treated with antimuscarinic drugs and an increased risk of a dementia diagnosis, although short-term data suggest that newer OAB antimuscarinics are cognitively safe. This study examined the cognitive safety of fesoterodine in older adults with mild cognitive impairment (MCI) and OAB. METHODS: This four-way randomised crossover study examined the cognitive effects of fesoterodine 4 and 8 mg and oxybutynin 5 mg b.i.d. compared with placebo. Older adult patients with OAB and MCI were included. Treatment and washout periods were of 1-week duration, to reach steady-state drug levels. The primary outcome was continuity of attention at 1 and 4 h after the dose. The secondary outcomes included other cognitive domains, change in Montreal Cognitive Assessment score, and alertness. KEY FINDINGS AND LIMITATIONS: Twenty-three patients completed the study (16 females and seven males). For the primary outcome, at 1 h after the dose, a trend towards worsening of continuity of attention was observed for fesoterodine 4 mg (p = 0.09) compared with placebo. At 4 h after the dose, a nonstatistically significant trend towards improvement compared with placebo was observed in the fesoterodine 4 mg group (p = 0.0633) compared with placebo. No differences were observed in any other treatment group at either time point. Apart from quality of working memory, associated with a statistically significant improvement with fesoterodine 4 mg, there was no difference in any comparison for other secondary outcomes. CONCLUSIONS: Exposure to steady-state dosing of fesoterodine 4 and 8 mg or oxybutynin 5 mg b.i.d. was not associated with any detectable effect on cognitive function using a sensitive battery of cognitive tests in a group of older adult patients with MCI and OAB. PATIENT SUMMARY: In this report, we investigated whether the medication fesoterodine, a member of a family of drugs called anticholinergics, commonly used for the treatment of a condition called overactive bladder that leads to accidental leakage of urine, affected the memory function of older adults with mild memory impairment. These people might be more sensitive to memory side effects. We found that at the doses most used by doctors, the drug had no effect on any of the memory functions we tested.


Asunto(s)
Compuestos de Bencidrilo , Cognición , Disfunción Cognitiva , Estudios Cruzados , Ácidos Mandélicos , Antagonistas Muscarínicos , Vejiga Urinaria Hiperactiva , Humanos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/farmacología , Femenino , Masculino , Anciano , Disfunción Cognitiva/tratamiento farmacológico , Método Doble Ciego , Ácidos Mandélicos/uso terapéutico , Ácidos Mandélicos/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/uso terapéutico , Anciano de 80 o más Años , Cognición/efectos de los fármacos , Esquema de Medicación
5.
J Clin Pharmacol ; 61(7): 961-971, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33368382

RESUMEN

Oxybutynin is a racemic anticholinergic drug used for the symptomatic treatment of detrusor overactivity. The formation of active metabolites related to tolerability problems depends on the route of administration. The objective of this evaluation was to develop a pharmacokinetic model for oral/intravesical administration as the basis for simulations with different dosages. Data from a published changeover clinical study with 18 healthy adults receiving a single oral dose of 5 mg immediate-release oxybutynin and single and multiple intravesical doses of 10 mg oxybutynin solution was evaluated. Enantioselective plasma concentrations of oxybutynin and N-desethyloxybutynin (NDO) were used to establish a population pharmacokinetic model using nonlinear mixed-effects modeling with NONMEM 7.4.1. For both enantiomers, the data were described well by a 2-compartment model for oxybutynin with an additional compartment for NDO. Oxybutynin absorption was modeled by transit compartments for oral and first-order absorption for intravesical application. Bioavailability of the more active (R)-enantiomer was 7% for oral and 10%-22% for intravesical administration. In simulations, intravesical doses of 5 to 15 mg (R)-oxybutynin administered 2 to 3 times daily decreased peak-trough fluctuations of NDO to 8% compared with 24% after oral administration. The NDO/oxybutynin ratio was reduced from 17 after oral administration to unity. Chronic intravesical versus oral administration of (R)-oxybutynin generates distinctly lower and less variable concentrations of (R)-NDO. Pharmacokinetic simulations suggest that exposure for 12.5 mg (R)-oxybutynin administered twice daily might not compromise efficacy and tolerability compared with exposure for standard thrice-daily administrations. This assumption needs to be assessed in clinical studies.


Asunto(s)
Antagonistas Colinérgicos/química , Antagonistas Colinérgicos/farmacocinética , Ácidos Mandélicos/química , Ácidos Mandélicos/farmacocinética , Administración Intravesical , Administración Oral , Área Bajo la Curva , Antagonistas Colinérgicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Voluntarios Sanos , Humanos , Ácidos Mandélicos/administración & dosificación , Ácidos Mandélicos/metabolismo , Tasa de Depuración Metabólica , Modelos Biológicos
7.
Int J Dermatol ; 59(6): 709-715, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32301117

RESUMEN

BACKGROUND: Hyperhidrosis (HH) is characterized by exaggerated sweating in a specific region due to hyperfunction of the sweat glands. In the late 2000s, we started treating patients with an anticholinergic, oxybutynin, that was not being used until then. OBJECTIVES: To present, after 12 years of utilizing this medication in our service, the substantial experience obtained with the use of oxybutynin as an initial treatment of HH in a large series of 1,658 patients. METHODS: We analyzed 1,658 patients treated with oxybutynin for HH from May 2006 to June 2018. The patients were divided into four groups according to the main site of HH: the plantar group, the axillary group, the facial group, and the palmar group. To measure the degree of satisfaction, a quality of life (QoL) questionnaire was used. RESULTS: Pre-treatment QoL was poor or very poor in more than 94% of the cases, and the palmar group had the worst quality of life. After treatment, we observed an improvement in the quality of life in 77% of patients. More than 70% of the patients in all groups present moderate or optimal subjective clinical improvement in sweating after treatment. The group with the best result was the facial group. Intense dry mouth was reported in 24.9% of all patients in all groups. CONCLUSIONS: This study included a large number of patients followed for a long period and demonstrated the good effectiveness of treatment with oxybutynin for hyperhidrosis in the main sites of sweating.


Asunto(s)
Hiperhidrosis/tratamiento farmacológico , Ácidos Mandélicos/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Calidad de Vida , Xeroftalmia/epidemiología , Administración Oral , Adolescente , Adulto , Axila , Esquema de Medicación , Cara , Femenino , Estudios de Seguimiento , Mano , Humanos , Hiperhidrosis/diagnóstico , Hiperhidrosis/psicología , Masculino , Ácidos Mandélicos/efectos adversos , Persona de Mediana Edad , Antagonistas Muscarínicos/efectos adversos , Satisfacción del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios/estadística & datos numéricos , Factores de Tiempo , Resultado del Tratamiento , Xeroftalmia/inducido químicamente , Xeroftalmia/diagnóstico , Adulto Joven
8.
J Urol ; 203(4): 826-831, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31821098

RESUMEN

PURPOSE: We studied the effect of oxybutynin on bladder and upper urinary tract outcomes in infants following posterior urethral valve ablation. MATERIALS AND METHODS: Patients younger than 12 months old who had undergone primary endoscopic valve ablation for posterior urethral valves were screened for eligibility. Patients who had undergone urinary diversion or had other conditions that could affect lower urinary tract function were excluded. Study patients were randomized to either oxybutynin (0.2 mg/kg 3 times daily) until toilet training or active observation. The study end points were serum creatinine, estimated glomerular filtration rate, hydronephrosis improvement, vesicoureteral reflux resolution, febrile urinary tract infection and toilet training. RESULTS: A total of 49 infants (24 receiving oxybutynin and 25 undergoing observation) were enrolled between December 2013 and September 2015 and completed at least 1 year of followup. Oxybutynin was discontinued before toilet training in 5 patients due to facial flushing in 2, bladder and upper tract dilatation in 2, and cognitive changes in 1. After a median followup of 44.2 months (range 12 to 57.6) median serum creatinine and estimated glomerular filtration rate were not significantly different between the groups (p=0.823 and p=0.722, respectively). Renal units in the oxybutynin group had a greater likelihood of hydronephrosis improvement (61.9% vs 34.8%, p=0.011) and resolution of vesicoureteral reflux (62.5% vs 25%, p=0.023). Febrile urinary tract infection (29.2% vs 40%, p=0.404), completion of toilet training (70.8% vs 76%, p=0.748) and age at toilet training (p=0.247) did not differ significantly between the oxybutynin and observation groups. CONCLUSIONS: Oxybutynin enhances hydronephrosis improvement and vesicoureteral reflux resolution following primary endoscopic valve ablation in infants but periodic monitoring is warranted.


Asunto(s)
Hidronefrosis/terapia , Ácidos Mandélicos/administración & dosificación , Uretra/anomalías , Obstrucción Uretral/cirugía , Agentes Urológicos/administración & dosificación , Reflujo Vesicoureteral/terapia , Creatinina/sangre , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Humanos , Hidronefrosis/etiología , Hidronefrosis/fisiopatología , Lactante , Recién Nacido , Riñón/efectos de los fármacos , Riñón/fisiopatología , Masculino , Resultado del Tratamiento , Obstrucción Uretral/etiología , Obstrucción Uretral/fisiopatología , Reflujo Vesicoureteral/etiología , Reflujo Vesicoureteral/fisiopatología
9.
J Cosmet Dermatol ; 19(2): 393-399, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31553119

RESUMEN

BACKGROUND: Chemical peels have become a popular modality in the treatment of acne vulgaris (AV). Mandelic acid (MA) is a new emerging peeling agent for AV owing to its antibacterial and anti-inflammatory properties. Hence, it is worthwhile to evaluate the effectiveness and safety profile of this newer agent and to compare it with an older established peeling agent, salicylic acid (SA) in the treatment of AV. OBJECTIVE: Comparison between therapeutic efficacy and safety of 45% MA peel with 30% SA peel in Indian patients suffering from mild-to-moderate facial AV. METHODS: A total of 50 patients suffering from mild-to-moderate AV were randomly divided into two groups, with one receiving 30% SA peels and the other receiving 45% MA peels at an interval of 2 weeks for six sessions. Total duration of the study was 12 weeks. Michaelsson acne scores (MAS) and clinical photographs were used to evaluate the efficacy of therapy objectively. Adverse effects of both the agents were also noted at each visit. RESULTS: Both agents showed almost equal efficacy in improving mild-to-moderate AV. Salicylic acid was found better in treating noninflammatory lesions, while MA had an upper hand in treating inflammatory lesions. Overall, there was no significant difference between the two peels in improving MAS and percentage decrease in MAS. However, adverse effects were lesser with MA peels. CONCLUSION: About 45% MA peel was found to be equally effective as 30% SA peel in mild-to-moderate facial AV. However, safety and tolerability of MA peel were better than SA peel.


Asunto(s)
Acné Vulgar/terapia , Quimioexfoliación/métodos , Queratolíticos/administración & dosificación , Ácidos Mandélicos/administración & dosificación , Ácido Salicílico/administración & dosificación , Acné Vulgar/diagnóstico , Adolescente , Quimioexfoliación/efectos adversos , Relación Dosis-Respuesta a Droga , Cara , Femenino , Humanos , Queratolíticos/efectos adversos , Masculino , Ácidos Mandélicos/efectos adversos , Estudios Prospectivos , Ácido Salicílico/efectos adversos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
10.
Drug Test Anal ; 11(11-12): 1755-1760, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31670462

RESUMEN

According to class M2.1 of the World Anti-Doping Agency (WADA) Prohibited List, the manipulation of doping control urine samples to alter their integrity and validity is prohibited both in- and out-of-competition. However, some paraplegic athletes with an overactive bladder need to be regularly treated with anti-cholinergic and anti-spasmodic drugs such as oxybutynin, which are often administered intravesically to reduce the substantial side effects observed after oral application. So far, it remains unclear whether such bladder instillations have a negative impact on analytical procedures and thus represent an anti-doping rule violation. Within this pilot study, urine samples were collected from five paraplegic athletes before and after an intravesical oxybutynin hydrochloride instillation. The samples were routinely tested for the presence of performance-enhancing drugs and afterwards fortified with 25 model compounds representing different classes of doping agents (anabolic agents, cannabinoids, diuretics, glucocorticoids, hormone and metabolic modulators, and stimulants) at low and medium concentrations. Additionally, the pH value and specific gravity were measured and the presence of oxybutynin was qualitatively determined by gas chromatography-mass spectrometry (GC-MS). In initial testing procedures, all samples were tested negative. Oxybutynin was present in most of the samples but found to have no significant effect on the detectability of the 25 model compounds subsequently added to each urine specimen. Therefore, it can be concluded that intravesical instillations with oxybutynin hydrochloride do not alter the integrity and validity of doping control urine samples.


Asunto(s)
Ácidos Mandélicos/orina , Sustancias para Mejorar el Rendimiento/orina , Detección de Abuso de Sustancias/métodos , Urinálisis/métodos , Agentes Urológicos/orina , Administración Intravesical , Doping en los Deportes , Femenino , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Masculino , Ácidos Mandélicos/administración & dosificación , Proyectos Piloto , Agentes Urológicos/administración & dosificación
11.
PLoS Med ; 16(10): e1002930, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31634354

RESUMEN

BACKGROUND: Desmopressin was approved by the Food and Drug Administration (FDA) in 1978 for use in diabetes insipidus and bleeding disorders, but it is also prescribed off-label for patients with nocturia. Quantifying the potential risks facing adult patients taking desmopressin has taken on added importance because a new intranasal formulation of desmopressin was approved by the FDA in 2017. Like the old formulation, the main active ingredient is desmopressin acetate, but the new formulation also contains an excipient designed to enhance absorption. Our objective was to quantify the rate of hyponatremia in routine clinical care for patients prescribed the older formulation of desmopressin. METHODS AND FINDINGS: We conducted a population-based new-user cohort study from 1 February 2006 to 1 February 2017 using a nationwide commercial health plan database. Patients newly prescribed the older formulation of desmopressin were propensity-score (PS)-matched to patients newly prescribed oxybutynin. As a sensitivity analysis, tamsulosin was used as the comparator rather than oxybutynin. The primary outcome was a primary position diagnosis of hyponatremia. Proportional hazard models after 1:1 PS matching were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). We identified 3,137 adults who were newly prescribed desmopressin and matched them to 3,137 adults who were newly prescribed oxybutynin. Mean age was 70, 55% were male, 13% filled a prescription for a diuretic during the baseline time period, and the mean baseline sodium prior to receiving either study drug was 140 mmol/L (normal: 135-145). The rate of hyponatremia was 146 per 1,000 person-years for adults prescribed desmopressin compared to 11 per 1,000 person-years for adults prescribed oxybutynin, corresponding to a 13-fold higher rate (HR 13.19; 95% CI 6.69, 26.01; p < 0.01). When follow-up was truncated at 30 days, a similar increased rate was observed (HR 19.41; 95% CI 7.11, 52.99; p < 0.01). A higher rate of hyponatremia was also observed with desmopressin when tamsulosin was the comparator (HR 12.10; 95% CI 6.54, 22.37; p < 0.01). Important limitations of our study include unmeasured confounding (for example, over-the-counter medication use, dietary intake), missing data (i.e., only 20% of patients had a baseline serum sodium), and a lack of data on the newer formulation of desmopressin. CONCLUSIONS: Use of an older formulation of desmopressin was associated with a marked increased rate of subsequent hyponatremia compared to use of other medications indicated for lower urinary tract symptoms. Such risks should be clearly communicated to patients prescribed this formulation of desmopressin.


Asunto(s)
Desamino Arginina Vasopresina/efectos adversos , Hemostáticos/efectos adversos , Hiponatremia/inducido químicamente , Administración Intranasal , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Ácidos Mandélicos/administración & dosificación , Persona de Mediana Edad , Nocturia/tratamiento farmacológico , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Factores de Riesgo , Tamsulosina/administración & dosificación , Resultado del Tratamiento
12.
Urol Int ; 103(2): 202-210, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31117096

RESUMEN

PURPOSE: A low-pressure bladder in children with neuropathic bladder dysfunction can be achieved using anticholinergic medication. Due to the significant side effects of oral oxybutynin, our patients are treated with daily intravesical oxybutynin instillations. Newer oral anticholinergic medication, such as fesoterodine, claim to have fewer side effects in a once daily formulation. Because once-daily oral intake is easier than performing twice-daily intravesical instillations, we studied the effects of switching from intravesical oxybutynin to oral fesoterodine and compared the clinical response, urodynamic parameters and side effects. PATIENTS AND METHODS: Twenty children (11 girls, 9 boys, 4-17 years) with neuropathic bladder dysfunction who perform clean intermittent catheterization and use intravesical oxybutynin instillations twice daily were included in this prospective study. Voiding diaries, a behavioural checklist, urodynamic investigations, vital signs and blood samples were evaluated at baseline during treatment with intravesical oxybutynin and repeated after 40 days of oral fesoterodine. RESULTS: Out of 20, 13 (65%) children showed an identical objective dryness (pad-test), 2 (10%) improved and 5 (25%) got worse. Seven (35%) children reported equal dryness, 7 (35%) reported improvement and 6 (30%) reported that it got worse. From a urodynamic perspective, 13 (65%) children remained identical, 3 (15%) improved and 4 (20%) got worse. Four (20%) children reported a light to moderate dry mouth, 1 (5%) a headache, 1 (5%) behavioural changes during fesoterodine administration, 1 (5%) an increased appetite, 1 (5%) nausea and 1 (5%) hot flushes. CONCLUSIONS: The urodynamics after 40 days of fesoterodine were in 16 (80%) identical or better and could be a safe alternative for oxybutynin instillations in children with neuropathic bladder dysfunction.


Asunto(s)
Compuestos de Bencidrilo/administración & dosificación , Sustitución de Medicamentos , Ácidos Mandélicos/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Administración Intravesical , Administración Oral , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Prospectivos
15.
Biol Pharm Bull ; 42(4): 586-593, 2019 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-30686806

RESUMEN

The combination of skin external preparation and transdermal patch is influenced by drug absorption through the skin. We investigated the effect of heparinoid cream on the transdermal absorption of oxybutynin hydrochloride using an oxybutynin transdermal patch and determined the combined effect of these medications. Normal skin and dry dorsal skin in hairless mice were treated with heparinoid cream, followed by the application of the oxybutynin transdermal patch. A blood sample was collected from the mouse tail vein and the blood concentration of oxybutynin hydrochloride was analyzed by LC-MS/MS. Transepidermal water loss, the hydration level of the stratum corneum, and the stratum corneum thickness in the dorsal skin were measured. The blood concentration and area under the curve (AUC)0→24 of oxybutynin hydrochloride increased when the 4.0-cm2 oxybutynin transdermal patch was applied 1 h after the application of the moisturizer, compared to the values without moisturizer. Normal skin and dry skin did not affect this result. As the hydration level of the stratum corneum and stratum corneum thickness increased before patch application by pre-treatment with moisturizer, it was suggested that transdermal absorption of oxybutynin hydrochloride was increased by skin hydration. The increased blood concentration of oxybutynin hydrochloride was regulated by changing the effective area of the patch and applying additional moisturizer at intervals. The pharmacokinetics of oxybutynin hydrochloride under the regulation of combination treatment was similar to that of treatment without moisturizer. These findings indicate that the application conditions of the oxybutynin transdermal patch and heparinoid cream influence the proper use of the patch.


Asunto(s)
Heparinoides/farmacología , Ácidos Mandélicos/sangre , Crema para la Piel/farmacología , Parche Transdérmico , Agentes Urológicos/sangre , Animales , Heparinoides/administración & dosificación , Masculino , Ácidos Mandélicos/administración & dosificación , Ácidos Mandélicos/efectos adversos , Ratones Pelados , Piel/metabolismo , Absorción Cutánea/efectos de los fármacos , Crema para la Piel/administración & dosificación , Agentes Urológicos/administración & dosificación , Agentes Urológicos/efectos adversos
16.
Biomed Chromatogr ; 33(4): e4456, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30536598

RESUMEN

A rapid, selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed to simultaneously determine oxybutynin and its active metabolite N-desethyl oxybutynin in rat plasma. A 0.1 mL sample of plasma was extracted with n-hexane. Chromatographic separation was performed on a UPLC BEH C18 column (2.1 × 100 mm i.d.,1.7 µm) with mobile phase of methanol-water (containing 2 mmol/L ammonium acetate and 0.1% formic acid; 90:10, v/v). The detection was performed in positive selected reaction monitoring mode. Each plasma sample was chromatographed within 3 min. The linear calibration curves were obtained in the concentration range of 0.0944-189 ng/mL (r ≥ 0.99) for oxybutynin and 0.226-18.0 ng/mL (r ≥ 0.99) for N-desethyl oxybutynin. The intra- and inter-day precision (relative standard deviation) values were not more than 14% and the accuracy (relative error) was within ±7.6%. The method described was superior to previous methods for the quantitation of oxybutynin with three product ions and was successfully applied to a pharmacokinetic study of oxybutynin and its active metabolite N-desethyl oxybutynin in rat plasma after transdermal administration.


Asunto(s)
Ácidos Mandélicos/sangre , Ácidos Mandélicos/farmacocinética , Parche Transdérmico , Animales , Cromatografía Líquida de Alta Presión/métodos , Límite de Detección , Modelos Lineales , Masculino , Ácidos Mandélicos/administración & dosificación , Ácidos Mandélicos/química , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodos
17.
Eur Urol Focus ; 5(6): 1112-1119, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29625926

RESUMEN

Overactive bladder syndrome (OAB) is a prevalent disorder with a significant impact on quality of life. Despite this high prevalence, there is significant underdiagnosis and undertreatment due to several barriers, including embarrassment, poor communication and low patient adherence. Currently, various antimuscarinic are available in the treatment of OAB. The introduction of mirabegron has broadened the therapeutic approach and combination therapy of both agents can be valuable in clinical practice. Yet, patient adherence to most drugs for OAB is still relatively poor. Healthcare providers need to identify and utilise strategies to improve treatment adherence by defining clear treatment goals, implement educational methods and frequently communicate with patients to identify problems with adherence. The elderly population form need special attention as in these patients, anticholinergics should be prescribed with care and adequate knowledge regarding pharmacokinetics and drug interactions in essential. Furthermore, patient expectations should be clearly discussed. In this narrative review, the current advances in oral pharmacotherapy are evaluated and the most important factors involved in the management of OAB are discussed.


Asunto(s)
Acetanilidas/administración & dosificación , Acetanilidas/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 3/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 3/uso terapéutico , Tiazoles/administración & dosificación , Tiazoles/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Acetanilidas/efectos adversos , Administración Oral , Agonistas de Receptores Adrenérgicos beta 3/efectos adversos , Anciano , Estudios de Casos y Controles , Antagonistas Colinérgicos/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Masculino , Ácidos Mandélicos/administración & dosificación , Ácidos Mandélicos/efectos adversos , Ácidos Mandélicos/uso terapéutico , Persona de Mediana Edad , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/efectos adversos , Antagonistas Muscarínicos/uso terapéutico , Cooperación del Paciente/estadística & datos numéricos , Prevalencia , Calidad de Vida , Tiazoles/efectos adversos , Vejiga Urinaria Hiperactiva/epidemiología , Vejiga Urinaria Hiperactiva/psicología
18.
Actas Urol Esp (Engl Ed) ; 43(3): 143-150, 2019 Apr.
Artículo en Inglés, Español | MEDLINE | ID: mdl-30470585

RESUMEN

INTRODUCTION AND OBJECTIVES: Older patients with overactive bladder under antimuscarinic treatment are especially susceptible to cognitive impairment. The aim was to assess short term changes in cognitive function in elderly patients with overactive bladder treated with transdermal oxybutynin. MATERIALS AND METHODS: Observational, retrospective, multicentre study in patients with overactive bladder aged 65-80 years undergoing treatment with transdermal oxybutynin. Before and after one month of treatment, cognitive function using the Memory Alteration Test and Clock-Drawing Test, changes in symptoms with validated questionnaires, patient perception of treatment response using Treatment Benefit Scale and treatment adherence with the modified Morisky-Green test, were assessed. RESULTS: From 85 eligible patients, 70 completed the assessment (mean age: 71.4±4.5; BMI: 28.7±3.1kg/m2). No cognitive impairment was observed after one month with transdermal oxybutynin: Memory Alteration Test (+1 point; 95%CI: 0.0-1.5), Clock-Drawing Test (0 points; 95%CI: 0.0-0.0). A statistically significant improvement (P<.001) was observed in all urinary storage symptoms, except stress urinary incontinence. There was an improvement in the Bladder Control Self-Assessment Questionnaire (symptom score: -2.27; 95%CI: -2.8, -1.7; P<.001; bother score: -2.73; 95%CI: -3.3, -2.1; P<.001). 70% of patients reported either a stable or improved bladder condition according to the Patient Perception of Bladder Condition questionnaire. 72.8% of patients reported that their urinary problems had improved or greatly improved with an 84.3% treatment adherence. CONCLUSIONS: No cognitive impairment was observed in elderly patients after one month of treatment with transdermal oxybutynin; urinary urgency symptoms improved and there was adequate treatment adherence.


Asunto(s)
Cognición , Ácidos Mandélicos/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/psicología , Administración Cutánea , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Pruebas Psicológicas , Estudios Retrospectivos
20.
Einstein (Sao Paulo) ; 16(3): eAO4207, 2018 Aug 06.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-30088545

RESUMEN

OBJECTIVE: To prospectively compare the results of intradetrusor onabotulinumtoxinA injections and oral oxybutynin for urinary continence, urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity due to spinal cord injury. METHODS: Adult patients under intermittent catheterization were randomized 1:1 to receive one injection of onabotulinumtoxinA 300U or oxybutynin 5mg, per oris, three times/day. Primary study endpoint was change in urinary incontinence episodes/24 hours and secondary study endpoints were maximum cystometric capacity, maximum detrusor pressure, bladder compliance and quality of life before randomization and at week 24. RESULTS: Sixty-eight patients participated in the trial. Significant improvements in urinary incontinence per 24 hours, all investigated urodynamic parameters and quality of life were observed in both groups. Compared with oral oxybutynin, onabotulinumtoxinA was significantly more efficacious for all parameters investigated. Non-response to treatment was higher for oral oxybutynin (23.5%) than onabotulinumtoxinA (11.8%). Dry mouth was the most common adverse in patients with oral oxybutynin (72%) and transient macroscopic hematuria in patients with onabotulinumtoxinA (28%). Only one patient with oral oxybutynin dropped out the study because of adverse effects. CONCLUSION: The comparison of the two study drugs showed that onabotulinumtoxinA was significantly more efficacious than oral oxybutynin with regard to continence, urodynamic parameters and quality of life. Clinicaltrials.gov: NCT:01477736.


Asunto(s)
Inhibidores de la Liberación de Acetilcolina/administración & dosificación , Toxinas Botulínicas Tipo A/administración & dosificación , Ácidos Mandélicos/administración & dosificación , Traumatismos de la Médula Espinal/complicaciones , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Administración Oral , Adulto , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intramusculares , Masculino , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Hiperactiva/etiología
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