RESUMEN
The purpose of this work was to elaborate a diagnosis of the dissolution test in Africa in comparison with Brazil, evaluating the dissolution profile of low solubility drugs such as albendazole, ibuprofen, furosemide, glibenclamide, hydrochlorothiazide and carvedilol to ascertain their quality. The dissolution profiles were evaluated by utilizing the United States Pharmacopeia (USP). The glibenclamide medicine was evaluated according to the Food and Drug Administration (FDA), while a dissolution method was developed for the carvedilol medicine. A filter selection test for all the drugs showed that cannula is suitable for all, except for carvedilol, which is centrifuged. The various brands of Nigerian and Brazilian medicines tested showed some statistical differences. The suitable conditions that allowed the dissolution of carvedilol to be determined were the USP type II apparatus at 75 rpm containing 900 mL of acetate buffer, pH 4.5. The results of the dissolution test showed that out of the 17 different brands of Brazilian medicines and 17 different products from Nigeria, 94.12% and 58.82% passed respectively
O objetivo deste trabalho foi elaborar um diagnóstico do teste de dissolução na África em comparação ao Brasil, avaliando o perfil de dissolução de medicamentos de baixa solubilidade como albendazol, ibuprofeno, furosemida, glibenclamida, hidroclorotiazida e carvedilol para verificar sua qualidade.Os perfis de dissolução foram avaliados utilizando a Farmacopeia dos Estados Unidos (USP). O medicamento glibenclamida foi avaliado de acordo com a Food and Drug Administration (FDA), enquanto um método de dissolução foi desenvolvido para o medicamento carvedilol.Um teste de seleção de filtro para todos os medicamentos mostrou que a cânula é adequada para todos, exceto para o carvedilol, que é centrifugado. As diversas marcas de medicamentos Nigerianos e Brasileiros testadas apresentaram algumas diferenças estatísticas. As condições adequadas que permitiram a determinação da dissolução do carvedilol foram o aparelho USP tipo II a 75 rpm contendo 900 mL de tampão acetato, pH 4,5. Os resultados do teste de dissolução mostraram que das 17 diferentes marcas de medicamentos brasileiros e 17 diferentes produtos da Nigéria, 94,12% e 58,82% foram aprovados, respectivamente
Asunto(s)
Solubilidad , Brasil/etnología , Preparaciones Farmacéuticas/análisis , África/etnología , Disolución , United States Food and Drug Administration , Albendazol/farmacología , Ibuprofeno , Carvedilol/farmacología , Furosemida/farmacología , Métodos , Acetatos/efectos adversosRESUMEN
Abstract Two sensitive and selective methods were developed for the simultaneous determination of four commonly used non-steroidal anti-inflammatory drugs (NSAIDs), namely; paracetamol (PCM), diclofenac sodium (DCF), ibuprofen (IBP), and indomethacin (IND) in wastewater effluents. The first method used HPLC for the determination of the studied drugs using a mobile phase consisting of phosphate buffer (pH 3.0) and acetonitrile at a flow rate of 1 mL/min. in gradient elution mode and detection at 220 nm. The separation process was performed on BDS Hypersil Cyano column (250 x 4.6 mm, 5 µm). The second method was a TLC-densitometric one which was performed using n-Hexane: ethyl acetate: acetic acid in the ratio (6:3.5:0.5) as a developing system. The proposed chromatographic methods were successfully applied for the selective determination of the four studied drugs in simulated and real pharmaceutical wastewater samples after their solid-phase extraction
Asunto(s)
Efluentes Industriales , Antiinflamatorios no Esteroideos/análisis , Industria Farmacéutica/clasificación , Aguas Residuales/parasitología , Cromatografía Líquida de Alta Presión/métodos , Acetatos/efectos adversosRESUMEN
El montelukast se utiliza ampliamente en el tratamiento de sibilancias recurrentes y/o asma. Están descritas numerosas reacciones adversas medicamentosas (RAM) en niños relacionadas con montelukast; se destacan las neuropsiquiátricas. Realizamos un estudio observacional, retrospectivo, descriptivo, sobre RAM relacionadas con montelukast. Entre enero de 2012 y diciembre de 2017, en la Unidad de Neumonología Pediátrica se trataron con Montelukast 348 pacientes; de ellos, 20 presentaron RAM. Los síntomas más frecuentes fueron insomnio (n = 7), hiperactividad (n = 4), pesadillas (n = 3), dolor abdominal (n = 2) y parestesias en extremidades (n = 2). Se presentaron desde días hasta meses tras iniciar el tratamiento, y desaparecieron tras su suspensión. Se destacan dos pacientes con parestesias en extremidades, síntoma no descrito antes en niños. El 5,7 % de los pacientes tratados con montelukast presentaron RAM que requirieron suspender el tratamiento. Los trastornos del sueño fueron los más frecuentes.
Montelukast is widely used in recurrent wheezing and/or asthma treatment. Several adverse drug reactions (ADRs) have been described in children related to montelukast. Neuropsychiatric reactions are one of the most important. We designed an observational, retrospective, descriptive study on ADRs related to montelukast in the Pediatric Pulmonology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain. Between January 2012 and December 2017, in the Pediatric Pulmonology Unit, 348 patients were treated with Montelukast; of them, 20 presented RAM. The main symptoms described were insomnia (n = 7), hyperactivity (n = 4), nightmares (n = 3), abdominal pain (n = 2) and paraesthesia in extremities (n = 2). They appeared from the first days to months after the start of treatment and disappeared after stopping it. Two patients presented limb paresthesia, not described previously in children. The 5.7 % of our patients treated with montelukast had ADRs that required treatment discontinuation. Sleep disorders were the most frequent.
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Quinolinas/efectos adversos , Sulfuros/efectos adversos , Antiasmáticos/efectos adversos , Antagonistas de Leucotrieno/efectos adversos , Ciclopropanos/efectos adversos , Acetatos/efectos adversos , Asma/tratamiento farmacológico , Trastornos del Sueño-Vigilia/inducido químicamente , Estudios RetrospectivosRESUMEN
Montelukast is widely used in recurrent wheezing and/or asthma treatment. Several adverse drug reactions (ADRs) have been described in children related to montelukast. Neuropsychiatric reactions are one of the most important. We designed an observational, retrospective, descriptive study on ADRs related to montelukast in the Pediatric Pulmonology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain. Between January 2012 and December 2017, in the Pediatric Pulmonology Unit, 348 patients were treated with Montelukast; of them, 20 presented RAM. The main symptoms described Reacciones adversas a montelukast: de la teoría a la práctica. Serie de casos Adverse drug reactions of montelukast: from theory to practice. Case report were insomnia (n = 7), hyperactivity (n = 4), nightmares (n = 3), abdominal pain (n = 2) and paraesthesia in extremities (n = 2). They appeared from the first days to months after the start of treatment and disappeared after stopping it. Two patients presented limb paresthesia, not described previously in children. The 5.7 % of our patients treated with montelukast had ADRs that required treatment discontinuation. Sleep disorders were the most frequent.
El montelukast se utiliza ampliamente en el tratamiento de sibilancias recurrentes y/o asma. Están descritas numerosas reacciones adversas medicamentosas (RAM) en niños relacionadas con montelukast; se destacan las neuropsiquiátricas. Realizamos un estudio observacional, retrospectivo, descriptivo, sobre RAM relacionadas con montelukast. Entre enero de 2012 y diciembre de 2017, en la Unidad de Neumonología Pediátrica se trataron con Montelukast 348 pacientes; de ellos, 20 presentaron RAM. Los síntomas más frecuentes fueron insomnio (n = 7), hiperactividad (n = 4), pesadillas (n = 3), dolor abdominal (n = 2) y parestesias en extremidades (n = 2). Se presentaron desde días hasta meses tras iniciar el tratamiento, y desaparecieron tras su suspensión. Se destacan dos pacientes con parestesias en extremidades, síntoma no descrito antes en niños. El 5,7 % de los pacientes tratados con montelukast presentaron RAM que requirieron suspender el tratamiento. Los trastornos del sueño fueron los más frecuentes.
Asunto(s)
Antiasmáticos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Acetatos/efectos adversos , Ciclopropanos , Humanos , Quinolinas , Estudios Retrospectivos , SulfurosRESUMEN
Imatinib mesylate is a small molecule used in cancer therapy as a thyrosine kinase inhibitor. Dexketoprofen trometamol is a non-steroidal anti-inflammatory drug that has seen use in cancer therapy in combination with an anticancer drug to minimize tumor size and to reduce pain in patients. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as potential model drugs to be used in combination. A new, simple and selective Ultra Performance Liquid Chromatography method was developed and validated to determine the drug substances in distilled water, in a pH 7.4 phosphate buffer and in Dulbecco's Modified Eagle Medium. The proposed method was developed using a BEH C-18 column with isocratic elution. A mixture of methanol:acetonitrile (80:20, v/v) and pH 9.5, 0.05 M ammonium acetate were (70:30, v/v) used as a mobile phase. Detection was carried out with a flow rate of 0.3 mL/min, a column temperature of 30°C and an injection volume of 20 µL. The method was validated considering linearity, accuracy, precision, specificity, robustness, detection limit and quantitation limit values, and was found to be linear in a range from 0.05 to 20.0 µg/mL for the three different media
Asunto(s)
Estudio de Validación , Mesilato de Imatinib/antagonistas & inhibidores , Preparaciones Farmacéuticas/análisis , Cromatografía Liquida/métodos , Acetatos/efectos adversos , NeoplasiasRESUMEN
OBJECTIVE: To examine the association between montelukast prescription and neuropsychiatric events in children with asthma. STUDY DESIGN: A matched, nested case-control design was used to identify cases and controls from a cohort of children aged 5-18 years with physician-diagnosed asthma from 2004 to 2015, in Ontario, Canada, prescribed an asthma maintenance medication. Cases were children with a hospitalization or emergency department visit for a neuropsychiatric event. Cases were matched to up to 4 controls on birth year, year of asthma diagnosis, and sex. The exposures were dispensed prescriptions for montelukast (yes/no) and number of dispensed montelukast prescriptions in the year before the index date. Conditional logistic regression was used to measure the unadjusted OR and aOR and 95% CIs for montelukast prescription and neuropsychiatric events. Covariates in the adjusted model included sociodemographic factors and measures of asthma severity. RESULTS: In total, 898 cases with a neuropsychiatric event and 3497 matched controls were included. Children who experienced a new-onset neuropsychiatric event had nearly 2 times the odds of having been prescribed montelukast, compared with controls (OR 1.91, 95% CI 1.15-3.18; P = .01). Most cases presented for anxiety (48.6%) and/or sleep disturbance (26.1%). CONCLUSIONS: Children with asthma who experienced a new-onset neuropsychiatric event had nearly twice the odds of having been prescribed montelukast in the year before their event. Clinicians should be aware of the association between montelukast and neuropsychiatric events in children with asthma, to inform prescribing practices and clinical follow-up.
Asunto(s)
Acetatos/efectos adversos , Antiasmáticos/efectos adversos , Asma/tratamiento farmacológico , Trastornos Mentales/inducido químicamente , Enfermedades del Sistema Nervioso/inducido químicamente , Quinolinas/efectos adversos , Acetatos/uso terapéutico , Adolescente , Antiasmáticos/uso terapéutico , Estudios de Casos y Controles , Niño , Preescolar , Ciclopropanos , Femenino , Humanos , Masculino , Quinolinas/uso terapéutico , SulfurosRESUMEN
BACKGROUND: Most international asthma guidelines recommend that children ≤5 years with asthma or recurrent wheezing be treated with daily low- moderate dose inhaled corticosteroids (ICS) as the preferred controller and leukotriene receptor antagonists (LTRA) as alternative therapy. There is no systematic review comparing the efficacy of ICS versus LTRA monotherapy in this age group. OBJECTIVE: To compare the efficacy of daily ICS versus LTRA in preschoolers with asthma or recurrent wheezing. METHODS: Randomized, prospective, controlled trials published by December 2017, with a minimum of 3-month therapy with daily ICS versus LTRA were identified. The co-primary outcomes were the number of wheezing episodes and daily symptom score. Secondary outcomes included unscheduled emergency visits, need of rescue systemic corticosteroids (SC), hospitalization for exacerbations, lung function, and adverse effects. RESULTS: Of 29 trials identified, six studies (n = 3204 patients, 62% males, age range: 6-54 months) met the inclusion criteria; two were at low risk of bias. Five pertained to children with asthma; one to those with recurrent wheezing. No outcomes were similarly reported in the six studies, preventing meta-analysis. Based on trials at lowest risk of bias and the largest open-labelled studies, ICS was associated with better control of symptoms and less exacerbations than LTRA. And also less need for rescue SC. Insufficient data of high quality prevented firm conclusions on other secondary outcomes. CONCLUSIONS: In preschoolers with asthma or recurrent wheezing, daily ICS appears more effective than daily LTRA for improving symptom control and decreasing exacerbations, particularly those requiring rescue SC, although the magnitude of benefit remains to be quantified.
Asunto(s)
Acetatos/uso terapéutico , Corticoesteroides/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Antagonistas de Leucotrieno/uso terapéutico , Quinolinas/uso terapéutico , Ruidos Respiratorios/efectos de los fármacos , Acetatos/administración & dosificación , Acetatos/efectos adversos , Administración por Inhalación , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Antiasmáticos/administración & dosificación , Antiasmáticos/efectos adversos , Asma/fisiopatología , Preescolar , Ciclopropanos , Quimioterapia Combinada , Hospitalización , Humanos , Lactante , Antagonistas de Leucotrieno/administración & dosificación , Antagonistas de Leucotrieno/efectos adversos , Estudios Prospectivos , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Recurrencia , SulfurosRESUMEN
OBJECTIVES: The phytohormone methyl jasmonate (MeJA) has been identified as a vital cell regulator in plants. This substance is analogous to eicosanoids and similar to that of anti-inflammatory prostaglandins. In animals and in animal cells, it displayed an efficient neuroprotective, anti-inflammatory and antioxidant action; while in tumoral strains, it demonstrates a potentially highly attractive mechanism of apoptosis induction through various cellular and molecular mechanisms. The aim of the present review was to explore two new hypotheses that explain the action of MeJA, a lipid phytohormone and its potentially anti-apoptotic mechanism for use as a therapeutic target for future treatment of Inflammatory bowel diseases (IBDs). KEY FINDINGS: Methyl jasmonate is a new candidate for the treatment of IBDs, modulating the expression of the major classes of caspase-type protease families that selectively act on the extrinsic and intrinsic pathways of the apoptotic process. Its action is based on the reduction of the expression in tumour necrosis factor tissue levels and the modulating action of reactive oxygen species production, acting only on the destruction of cells that express the diseased phenotype, and preserving cells that are not transformed. CONCLUSIONS: Methyl jasmonate may represent an alternative for the transduction processes of important signals in the cellular renewal of the intestinal mucosa.
Asunto(s)
Acetatos/uso terapéutico , Antiinflamatorios/uso terapéutico , Ciclopentanos/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Oxilipinas/uso terapéutico , Reguladores del Crecimiento de las Plantas , Acetatos/efectos adversos , Animales , Antiinflamatorios/efectos adversos , Apoptosis/efectos de los fármacos , Ciclopentanos/efectos adversos , Fármacos Gastrointestinales/efectos adversos , Humanos , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Oxilipinas/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The purpose of this study was to investigate the ultrastructural effects of lead on the kidney cortex of rats. Wistar Albino rats (180-200g body weight) were divided into a controlled and lead acetate-exposed group. Rats received lead acetate at 500 ppm in their drinking water for 60 days. Both groups were fed with the same standard food, but lead acetate was added to the drinking water. During the experimental period, blood samples were taken from the abdominal aorta of the anesthetised animals. At the end of exposure, body weight and blood lead levels were measured. The kidney tissue samples were prepared and analyzed by light and transmission electron microscopy. Cortical renal tubules show various degenerative changes with focal tubular necrosis invaded by inflammatory cells. The ultrastructural alterations found in lead acetate-treated rats were a diminution in the amount of filtration slits, increased fusion of foot processes in epithelial cells of the glomeruli, increase of lysosomal structures and pinocytic vesicles as well as large mitochondria in proximal tubule cells.
El propósito de este estudio fue investigar los efectos ultraestructurales del plomo en la corteza renal. Ratas Wistar albinas (180-200g de peso corporal) fueron divididas en grupo control y grupo experimental. Las ratas recibieron 500 ppm de acetato de plomo en el agua potable durante 60 días. Ambos grupos fueron alimentados con el mismo alimento estándar, pero acetato de plomo se le añadió al agua potable al grupo experimental. Durante el período experimental, se tomaron bajo anestesia muestras sanguíneas desde la parte abdominal de la aorta. Al final de la exposición, fueron medidos el peso corporal y los niveles de plomo en la sangre. Fueron preparadas las muestras de tejido renal y se analizaron mediante microscopía de luz y electrónica de transmisión. Los túbulos renales corticales mostraron varios cambios degenerativos con necrosis tubular focal invadida por células inflamatorias. Las alteraciones ultraestructurales encontradas en las ratas tratadas con acetato de plomo correspondieron a una disminución en la cantidad de ranuras de filtración, aumento de la fusión de los procesos podales en las células epiteliales de los glomérulos, aumento de la estructura lisosomal y las vesículas pinocíticas, así como grandes mitocondrias en las células del túbulo proximal.
Asunto(s)
Ratas , Corteza Renal/anatomía & histología , Corteza Renal , Corteza Renal/irrigación sanguínea , Corteza Renal/lesiones , Corteza Renal/ultraestructura , Plomo/administración & dosificación , Plomo/fisiología , Plomo/sangre , Plomo/toxicidad , Acetatos/efectos adversos , Acetatos/sangre , Acetatos/toxicidad , Ratas Wistar/anatomía & histología , Ratas Wistar/lesiones , Ratas Wistar/sangreRESUMEN
OBJECTIVE: To compare the efficacy of inhaled corticosteroids (ICS) versus montelukast (MONT) in schoolchildren and adolescents with mild-moderate persistent asthma. METHODS: Randomised, prospective, controlled trials published January 1996 to November 2009 with a minimum of 4 weeks of ICS versus MONT and of ICS versus MONT+ICS were retrieved through Medline, Embase and Central databases. The primary outcome was asthma exacerbations requiring systemic corticosteroids (AEX); secondary outcomes were pulmonary function, withdrawal/hospitalisation due to AEX, change in symptoms score, rescue-medication-free days, albuterol use, adverse effects and adherence. RESULTS: Of 124 studies identified, 18 studies (n=3757 patients) met criteria for inclusion (13 compared ICS vs MONT, 3 ICS vs MONT+ICS and 2 ICS vs MONT vs ICS+MONT). Patients receiving ICS showed a significantly lower risk for AEX than those with MONT (RR=0.83, 95% CI 0.72 to 0.96, p=0.01); post-hoc analysis suggests this effect was independent of quality, sponsorship and study duration. Children treated with ICS had a significant higher pulmonary function (final FEV1 % predicted, change from baseline FEV1 %, final morning peak expiratory flow (PEF)) and better clinical parameters (albuterol use, symptom score, rescue-medication-free days, withdrawals due to AEX) versus MONT. No significant difference in primary or secondary outcomes was found when MONT was added on to ICS versus ICS alone; however, these analyses were based on only two studies. CONCLUSIONS: Schoolchildren and adolescents with mild-moderate persistent asthma treated with ICS had less AEX and better lung function and asthma control than with MONT. There are insufficient data to determine whether the addition of MONT to ICS improves outcome.
Asunto(s)
Acetatos/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Quinolinas/uso terapéutico , Acetatos/efectos adversos , Adolescente , Antiasmáticos/efectos adversos , Asma/fisiopatología , Niño , Preescolar , Ciclopropanos , Quimioterapia Combinada , Volumen Espiratorio Forzado/efectos de los fármacos , Glucocorticoides/efectos adversos , Humanos , Ápice del Flujo Espiratorio/efectos de los fármacos , Quinolinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Sulfuros , Resultado del TratamientoRESUMEN
The aims of this study were: (1) to correlate surface (SH) and cross-sectional hardness (CSH) with microradiographic parameters of artificial enamel lesions; (2) to compare lesions prepared by different protocols. Fifty bovine enamel specimens were allocated by stratified randomisation according to their initial SH values to five groups and lesions produced by different methods: MC gel (methylcellulose gel/lactic acid, pH 4.6, 14 days); PA gel (polyacrylic acid/lactic acid/hydroxyapatite, pH 4.8, 16 h); MHDP (undersaturated lactate buffer/methyl diphosphonate, pH 5.0, 6 days); buffer (undersaturated acetate buffer/fluoride, pH 5.0, 16 h), and pH cycling (7 days). SH of the lesions (SH(1)) was measured. The specimens were longitudinally sectioned and transverse microradiography (TMR) and CSH measured at 10- to 220-microm depth from the surface. Overall, there was a medium correlation but non-linear and variable relationship between mineral content and radicalCSH. radicalSH(1) was weakly to moderately correlated with surface layer properties, weakly correlated with lesion depth but uncorrelated with integrated mineral loss. MHDP lesions showed the highest subsurface mineral loss, followed by pH cycling, buffer, PA gel and MC gel lesions. The conclusions were: (1) CSH, as an alternative to TMR, does not estimate mineral content very accurately, but gives information about mechanical properties of lesions; (2) SH should not be used to analyse lesions; (3) artificial caries lesions produced by the protocols differ, especially considering the method of analysis.
Asunto(s)
Cariogénicos/efectos adversos , Caries Dental/patología , Esmalte Dental/patología , Acetatos/efectos adversos , Resinas Acrílicas/efectos adversos , Anatomía Transversal , Animales , Apatitas/farmacología , Tampones (Química) , Fosfatos de Calcio/farmacología , Cariostáticos/farmacología , Bovinos , Caries Dental/metabolismo , Esmalte Dental/química , Difosfonatos/efectos adversos , Durapatita/efectos adversos , Fluoruros/farmacología , Geles , Dureza , Concentración de Iones de Hidrógeno , Ácido Láctico/efectos adversos , Metilcelulosa/efectos adversos , Microrradiografía , Distribución Aleatoria , Soluciones , Factores de Tiempo , Desmineralización Dental/patología , Remineralización DentalRESUMEN
BACKGROUND: Asthma control remains suboptimal in adults and children worldwide. Inhaled salmeterol/fluticasone propionate combination (SFC) and oral montelukast (MON) are 2 treatments available for childhood asthma. OBJECTIVE: This study, the PEdiatric Asthma Control Evaluation (PEACE), investigated the efficacy and tolerability of SFC compared with MON for the control of persistent asthma in children. METHODS: Children with asthma (forced expiratory volume in 1 second [FEV(1)] 55%-80% predicted; reversibility >or=12%) aged 6 to 14 years who were receiving only short-acting beta(2)-agonists entered a 2-week run-in period. Symptomatic patients (rescue use or symptoms during 4 of the last 7 days) were randomized to double-blind, double-dummy treatment with SFC 50/100 microg BID via multidose dry powder inhaler or MON 5-mg tablet QD for 12 weeks. The primary end point was change from baseline in morning peak expiratory flow (PEF). Efficacy assessments included lung function, asthma symptoms, rescue medication use, and asthma control. Tolerability was assessed by recording the number and type of adverse events (AEs) and the number of asthma exacerbations. RESULTS: Of 607 patients screened, 548 were randomized to treatment. The SFC group contained 281 patients and the MON group included 267. Demographic characteristics and baseline data were similar for both groups (mean age, 9.3 years for both groups; mean [SD] FEV(1), 1.49 [0.43] L in the SFC group and 1.48 [0.43] L in the MON group). There were more males in the MON group (179 [67%]) than in the SFC group (156 [56%]). The adjusted mean (SE) changes from baseline in morning PEF were 45.88 (2.82) L/min with SFC and 28.7 (2.86) L/min with MON (treatment difference, 17.16 L/min; 95% CI, 9.23-25.08; P < 0.001). Compared with MON, the SFC group had significantly more asthma symptom-free days (odds ratio [OR], 1.74; 95% CI, 1.07-2.82; P = 0.025), more rescue-free days (OR, 3.24; 95% CI, 2.09-5.02; P < 0.001), and more asthma-controlled weeks (difference in treatment medians over weeks 1-12, 16.77%; 95% CI, 8.3-16.77; P < 0.001). Both treatments were well tolerated, with a similar number of patients reporting AEs (SFC group, 155/281 [55%]; MON group, 153/267 [57%]); the most common AE in both groups was headache (SFC group, 66 [23%]; MON group, 72 [27%]). The mean exacerbation rates over 12 weeks (post hoc analysis) were 0.12 in the SFC group and 0.30 in the MON group (SFC/MON ratio, 0.40; 95% CI, 0.29-0.57; P < 0.001). CONCLUSIONS: In these children with uncontrolled asthma previously on short-acting beta(2)-agonist monotherapy (% predicted FEV(1) <80%, frequent asthma symptoms and rescue medication use), treatment with SFC was significantly more effective in improving morning PEF and other measures of asthma control and in decreasing exacerbation rates (in a post hoc analysis) than treatment with MON. The 2 drugs were both well tolerated, with similar numbers and types of AEs reported.
Asunto(s)
Acetatos/uso terapéutico , Albuterol/uso terapéutico , Androstadienos/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Quinolinas/uso terapéutico , Acetatos/administración & dosificación , Acetatos/efectos adversos , Administración por Inhalación , Administración Oral , Adolescente , Albuterol/administración & dosificación , Albuterol/efectos adversos , Androstadienos/administración & dosificación , Androstadienos/efectos adversos , Antiasmáticos/administración & dosificación , Antiasmáticos/efectos adversos , Broncodilatadores/administración & dosificación , Broncodilatadores/efectos adversos , Niño , Ciclopropanos , Método Doble Ciego , Combinación de Medicamentos , Femenino , Fluticasona , Humanos , Masculino , Ápice del Flujo Espiratorio , Estudios Prospectivos , Calidad de Vida , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , SulfurosRESUMEN
OBJECTIVE: To evaluate efficacy, safety, health outcomes, and cost-effectiveness of fluticasone propionate (FP) versus montelukast (MON) in 342 children (6 to 12 years of age) with persistent asthma. STUDY DESIGN: Randomized, double-blind, 12-week study of treatment with FP inhalation powder 50 mug twice daily or MON chewable 5 mg once daily for 12 weeks. RESULTS: Compared with MON, FP significantly increased mean percent change from baseline FEV1 (forced expiratory volume in 1 second) (P=.002), morning PEF (peak expiratory flow) (P=.004), evening PEF (P=.020), and percent rescue-free days (P=.002) at end point, and it significantly reduced nighttime symptom scores (P <.001) and mean total (P=.018), and nighttime (P <.001) albuterol use. Withdrawals from the study were more frequent with MON (21%) than with FP (13%). Adverse events (69% vs 71%) and mean end point to baseline 12-hour urinary cortisol excretion ratios were similar. Parents and physicians were more satisfied with FP treatment than with MON (P=.006 and P=.016, respectively, at Week 12). Mean total daily asthma-related cost per patient in the FP group was approximately one-third of that in the MON group ($1.25 vs $3.49). CONCLUSION: FP was significantly more effective than MON in improving pulmonary function, asthma symptoms, and rescue albuterol use. Both therapies had similar safety profiles. Parent- and physician-reported satisfaction ratings were higher with FP treatment, and asthma-related costs were lower.
Asunto(s)
Acetatos/uso terapéutico , Androstadienos/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Quinolinas/uso terapéutico , Acetatos/efectos adversos , Acetatos/economía , Androstadienos/efectos adversos , Androstadienos/economía , Antiasmáticos/efectos adversos , Antiasmáticos/economía , Asma/clasificación , Broncodilatadores/efectos adversos , Broncodilatadores/economía , Niño , Ciclopropanos , Método Doble Ciego , Femenino , Fluticasona , Humanos , Hidrocortisona/orina , Masculino , Quinolinas/efectos adversos , Quinolinas/economía , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Sulfuros , Resultado del TratamientoRESUMEN
The effects of gabapentin, 400 mg and 800 mg, on anxiety induced by simulated public speaking (SPS) were investigated. Thirty-two normal male volunteers (aged 17-30 years) had their anxiety and mood evaluated by self-scales [Visual Analogue Mood Scale (VAMS) and Profile of Mood State (POMS)] during the SPS procedure. Physiological measures (heart rate and blood pressure) were taken. Treatment with gabapentin at 800 mg attenuated the anxiety of subjects that had a decrease on the VAMS item calm-excite. In addition, volunteers that received gabapentin at 400 mg and 800 mg showed a decrease in the hostility score in POMS. Our results suggest, in agreement with other studies, an anxiolytic potential to gabapentin.
Asunto(s)
Acetatos/uso terapéutico , Aminas , Ansiolíticos/uso terapéutico , Ansiedad/tratamiento farmacológico , Ácidos Ciclohexanocarboxílicos , Habla , Ácido gamma-Aminobutírico , Acetatos/administración & dosificación , Acetatos/efectos adversos , Adolescente , Adulto , Ansiolíticos/administración & dosificación , Ansiolíticos/efectos adversos , Ansiedad/psicología , Presión Sanguínea , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Gabapentina , Frecuencia Cardíaca , Humanos , MasculinoRESUMEN
OBJECTIVE: We tested the hypothesis that adding montelukast to budesonide would improve asthma control in children with inhaled glucocorticoid-dependent persistent asthma. STUDY DESIGN: In a multicenter, randomized, double-blind, crossover study, we compared the benefit of adding montelukast, 5 mg, or placebo once daily to budesonide, 200 microg, twice daily. RESULTS: After a 1-month run-in with budesonide, 200 microg, twice daily, 279 children were randomized to montelukast or placebo. The mean +/- SD age was 10.4 +/- 2.2 years, the mean forced expiratory volume in 1 second (FEV(1)) was 77.7% +/- 10.6% predicted, and reversibility was 18.1% +/- 12.9%. Compared with adding placebo to budesonide, adding montelukast produced significant improvements in mean percent change from baseline FEV(1) (P =.062 [P =.010 for per-protocol analysis]), mean absolute change from baseline FEV(1) (P =.040), mean increase from baseline in morning (P =.023) and evening (P =.012) peak expiratory flows, decrease in exacerbation days by approximately 23% (P <.001), decreased beta2-agonist use (P =.013), and reduced blood eosinophil counts (P <.001). The treatments did not differ significantly with regard to safety. CONCLUSIONS: Montelukast, 5 mg, added to budesonide improved asthma control significantly, indicated by a small additive effect on lung function and a clinically relevant decrease in asthma exacerbation days.
Asunto(s)
Acetatos/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Quinolinas/uso terapéutico , Acetatos/administración & dosificación , Acetatos/efectos adversos , Antiasmáticos/administración & dosificación , Antiasmáticos/efectos adversos , Asma/fisiopatología , Budesonida/administración & dosificación , Budesonida/efectos adversos , Budesonida/uso terapéutico , Ciclopropanos , Método Doble Ciego , Quimioterapia Combinada , Volumen Espiratorio Forzado/fisiología , Humanos , Valor Predictivo de las Pruebas , Calidad de Vida , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Sulfuros , Resultado del TratamientoRESUMEN
This 6-month, open-label extension study of a previously described base study compared oral montelukast with inhaled beclomethasone in terms of safety, forced expiratory volume in one second (FEV1) measurements, parent and patient satisfaction with treatment, asthma-related medical resource utilization, school absenteeism, and parental work loss in children with asthma. A total of 124 of 266 asthmatic children, 6 to 11 years of age, who enrolled in the base study entered a 6-month open-label extension study (74 boys, 50 girls) and were re-randomized (2:1 ratio) to receive once-daily oral montelukast (n = 83) or inhaled beclomethasone 100 mcg three times daily (n = 41). Children were evaluated in the clinic prior to re-randomization (Month 0) and at regular visits at 1, 3, and 6 months. Children and their parents showed a significantly higher overall satisfaction for montelukast at 6 months than for inhaled beclomethasone (p = 0.001 and p < 0.05, respectively). According to parents, montelukast was more convenient (p < 0.001), less difficult to use (p = 0.005), and was used as instructed more of the time (p = 0.006) compared with beclomethasone. Oral corticosteroid use was similar in the montelukast (13% of patients) and beclomethasone (17%) treatment groups. The montelukast treatment group was more adherent with their regimen than the inhaled beclomethasone treatment group; almost twice as many children on montelukast compared with inhaled beclomethasone were highly compliant (82% versus 45%). The two study groups were similar with respect to overall safety, change in FEV1, asthma-related medical resource utilization, school absenteeism, and parental work loss. Montelukast represents a safe and effective asthma treatment regimen to which children with asthma are more likely to adhere.
Asunto(s)
Acetatos/uso terapéutico , Antiasmáticos/uso terapéutico , Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Beclometasona/uso terapéutico , Quinolinas/uso terapéutico , Acetatos/administración & dosificación , Acetatos/efectos adversos , Administración por Inhalación , Administración Oral , Adolescente , Antiasmáticos/administración & dosificación , Antiasmáticos/efectos adversos , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Asma/fisiopatología , Beclometasona/administración & dosificación , Beclometasona/efectos adversos , Niño , Estudios Cruzados , Ciclopropanos , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Recursos en Salud/estadística & datos numéricos , Humanos , Masculino , Cooperación del Paciente , Satisfacción del Paciente , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Sulfuros , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Montelukast is a specific antagonist of leukotrienes' receptors and constitutes a therapeutic option in controlling asthma. OBJECTIVES: To evaluate efficacy of montelukast in patients with persistent light asthma, persistent moderate asthma and exercise-induced asthma; to try to reduce or to eliminate doses of inhaled steroid; to reduce the use of short-action beta agonists and to assess its tolerability in pediatric patients. MATERIAL AND METHOD: 40 patients were studied, 17 female, with an age range from 4 to 11 years and a mean of 7 years. Stratification was made by GINA-established parameters. RESULTS: Steroid dose could be reduced in 88%, with definitive suspension in 66% of patients. Moreover, an improvement in reducing asthma stratification and the use of rescue drugs were registered. 62% of patients with exercise-induced asthma improved and there was a good tolerance with the same side effects.
Asunto(s)
Acetatos/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Quinolinas/uso terapéutico , Acetatos/efectos adversos , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Agonistas Adrenérgicos beta/administración & dosificación , Agonistas Adrenérgicos beta/uso terapéutico , Antiasmáticos/efectos adversos , Asma Inducida por Ejercicio/tratamiento farmacológico , Niño , Preescolar , Ciclopropanos , Evaluación de Medicamentos , Quimioterapia Combinada , Femenino , Volumen Espiratorio Forzado , Humanos , Antagonistas de Leucotrieno , Estudios Longitudinales , Masculino , Estudios Prospectivos , Quinolinas/efectos adversos , Sulfuros , Resultado del TratamientoRESUMEN
CONTEXT: Hyperphosphatemia has an important role in the development of bone and mineral abnormalities in end-stage renal disease (ESRD). OBJECTIVE: To compare the phosphorus binding power and the hypercalcemic effect of calcium acetate and calcium carbonate in hemodialysis patients. TYPE OF STUDY: Crossover, randomized, double-blind study. PLACE: A private hospital dialysis center. PARTICIPANTS: Fifty-two patients who were undergoing regular hemodialysis three times a week ([Ca++] dialysate = 3.5 mEq/L). PROCEDURES: Half of the patients were started on 5.6 g/day of calcium acetate and, after a 2 week washout period, received 6.2 g/day of calcium carbonate. The other half followed an inverse protocol. MAIN MEASUREMENTS: Clinical interviews were conducted 3 times a week to monitor for side effects. Determinations of serum urea, calcium, phosphorus, hematocrit, Kt/V and blood gas analysis were obtained before and after each treatment. RESULTS: Twenty-three patients completed the study. A significant increase in calcium plasma levels was only observed after treatment with calcium carbonate [9.34 mg/dl (SD 0.91) vs. 9.91 mg/dl (SD 0.79), P < 0.01]. The drop in phosphorus levels was substantial and significant for both salts [5.64 mg/dl (SD 1.54) vs. 4.60 mg/dl (SD 1.32), P < 0.01 and 5.89 mg/dl (SD 1.71) vs. 4.56 mg/dl (SD 1.57), P < 0.01, for calcium acetate and calcium carbonate respectively]. The percentage reduction in serum phosphorus (at the end of the study) per milliequivalent of salt administered per day tended to be higher with calcium acetate but statistical significance was not found. CONCLUSION: Calcium acetate can be a good alternative to calcium carbonate in the handling of hyperphosphatemia in ESRD patients. When calcium acetate is used, control of hyperphosphatemia can be achieved with a lower administration of calcium, perhaps with a lower risk of hypercalcemia.