RESUMEN
Nizatidine is an anti-secretogogue and a gastroprotective drug with a half-life of 1-2 h and is well absorbed in the stomach. This study aimed to optimize the process and develop floating microparticles of nizatidine that are based on low methoxyl pectin. Oil-in-oil dispersion method and Taguchi orthogonal array design were employed, and the prolonged residence time of the microparticles in the stomach was demonstrated. The constraints for independent variables, viz. A-polymer, B-internal solvent volume, C-surfactant, D-stirring rate and E-stirring time were set to generate the experimental runs. Particle size, percentage yield, micromeritic properties, entrapment efficiency, in vitro buoyancy and in vitro release were characterized. Surface morphology, zeta potential, in vitro release kinetics and in vivo floating performance of the optimized formulation was examined. The microparticles were free-flowing, irregular in shape and had a mean particle size distribution of 73-187 µ. Low methoxyl pectin played a predominant role in achieving buoyancy and optimum gastric retention for the modified release of the drug, suggesting Korsmeyer-Peppas model as the possible release mechanism. In vivo radiographic study in rabbits revealed that the drug was retained in the stomach for a period of 6 h. These results indicate that nizatidine floating microparticulate system provides modified drug release for the effective treatment of gastric ulcer
Asunto(s)
Animales , Masculino , Femenino , Conejos , Estómago/efectos de los fármacos , Nizatidina/antagonistas & inhibidores , Eficiencia/clasificación , Solventes/efectos adversos , Úlcera Gástrica/patología , Técnicas In Vitro/instrumentación , Preparaciones Farmacéuticas/administración & dosificación , Cinética , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Liberación de FármacosRESUMEN
OBJECTIVE: Weight gain is associated with treatment with many psychotropic agents. Nizatidine, H2 receptor antagonist, has been proposed to have weight-reducing effects. This was a 12-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of nizatidine in reducing/limiting weight gain in patients with schizophrenia who have been under treatment with olanzapine. METHOD: Patients receiving olanzapine (2 to 6 months) and weight gain > 5 percent of their body weight during olanzapine treatment were randomly assigned to receive nizatidine 600 mg or placebo for up to 12 weeks. Change in psychopathology was assessed using Brief Psychiatric Rating Scale scores from baseline to endpoint. Safety was assessed using the Safety Assessed Software, assessment of glucose and lipid blood levels, and treatment-emergent adverse events. RESULTS: Out of 54 patients enrolled in this analysis, 45 completed the protocol. The mean weight change prior randomization was 7.6 kg and 7.3 kg for those randomized to placebo and nizatidine, respectively (p = 0.828). Patients receiving placebo and nizatidine had a mean weight gain of 12.3 percent (0.7 kg) and 12 percent (1.1 kg) from baseline to endpoint, respectively (p = 0.9). Patients from both groups experienced a statistically significant decrease on the Brief Psychiatric Rating Scale mean score from baseline to endpoint. Treatment-emergent adverse events were reported by 18.5 percent and 25.9 percent on the placebo and nizatidine group, respectively. There were no statistically significant differences in glucose and lipid blood levels from baseline to endpoint and between groups. CONCLUSIONS: The concomitant use of olanzapine with nizatidine was not effective in controlling weight gain in patients who had previously gained weight during treatment with olanzapine when compared to placebo.
OBJETIVO: Ganho de peso está associado ao tratamento com inúmeros psicotrópicos. O uso de nizatidina, um antagonista H2, pode estar associado à redução de peso. Este foi um ensaio clínico aleatorizado, duplo-cego, controlado com placebo, de 12 semanas, desenhado para avaliar a eficácia da nizatidina em reduzir/limitar o ganho de peso em pacientes com esquizofrenia recebendo olanzapina. MÉTODO: Pacientes recebendo olanzapina (entre dois e seis meses) e com ganho de peso > que 5 por cento desde o inicio do tratamento foram aleatorizados para receber nizatidina 600 mg ou placebo. Alterações psicopatológicas foram avaliadas usando-se a Brief Psychiatric Rating Scale total. A segurança foi avaliada por meio da pontuação na Safety Assessed Software, avaliação dos valores de glicemia e lipídios e a incidência de eventos adversos decorrentes do tratamento. RESULTADOS: Dos 54 pacientes incluídos na análise, 45 completaram o protocolo. A alteração média de peso antes da aleatorização foi de 7,6 kg e 7,3 kg nos pacientes aleatorizados para placebo e nizatidina, respectivamente (p = 0,828). Pacientes recebendo placebo e nizatidina tiveram, respectivamente, ganho médio de peso de 12,3 por cento (7 kg) e 12 por cento (1,1 kg) ao longo do estudo (p = 0,9). Ambos os grupos apresentaram diminuição estatisticamente significativa na pontuação média da Brief Psychiatric Rating Scale. Eventos adversos emergentes do tratamento foram relatados por 18,5 por cento e 25,9 por cento dos pacientes recebendo placebo e nizatidina, respectivamente. Não houve diferença estatisticamente significativa nos níveis glicêmicos e lipídicos do início ao final do estudo ou entre os grupos de tratamento. CONCLUSÕES: Comparado ao placebo, o uso concomitante de olanzapina e nizatidina não foi eficaz em controlar o peso em pacientes com ganho prévio de peso durante o tratamento com olanzapina.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Antipsicóticos/efectos adversos , Benzodiazepinas/efectos adversos , /uso terapéutico , Nizatidina/uso terapéutico , Obesidad/prevención & control , Esquizofrenia/tratamiento farmacológico , Índice de Masa Corporal , Escalas de Valoración Psiquiátrica Breve , Método Doble Ciego , Graduación en Auxiliar de Enfermería , Obesidad/inducido químicamente , Placebos , Aumento de Peso/efectos de los fármacosRESUMEN
OBJECTIVE: Weight gain is associated with treatment with many psychotropic agents. Nizatidine, H2 receptor antagonist, has been proposed to have weight-reducing effects. This was a 12-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of nizatidine in reducing/limiting weight gain in patients with schizophrenia who have been under treatment with olanzapine. METHOD: Patients receiving olanzapine (2 to 6 months) and weight gain >or= 5% of their body weight during olanzapine treatment were randomly assigned to receive nizatidine 600 mg or placebo for up to 12 weeks. Change in psychopathology was assessed using Brief Psychiatric Rating Scale scores from baseline to endpoint. Safety was assessed using the Safety Assessed Software, assessment of glucose and lipid blood levels, and treatment-emergent adverse events. RESULTS: Out of 54 patients enrolled in this analysis, 45 completed the protocol. The mean weight change prior randomization was 7.6 kg and 7.3 kg for those randomized to placebo and nizatidine, respectively (p = 0.828). Patients receiving placebo and nizatidine had a mean weight gain of 12.3% (0.7 kg) and 12% (1.1 kg) from baseline to endpoint, respectively (p = 0.9). Patients from both groups experienced a statistically significant decrease on the Brief Psychiatric Rating Scale mean score from baseline to endpoint. Treatment-emergent adverse events were reported by 18.5% and 25.9% on the placebo and nizatidine group, respectively. There were no statistically significant differences in glucose and lipid blood levels from baseline to endpoint and between groups. CONCLUSIONS: The concomitant use of olanzapine with nizatidine was not effective in controlling weight gain in patients who had previously gained weight during treatment with olanzapine when compared to placebo.
Asunto(s)
Antipsicóticos/efectos adversos , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Nizatidina/uso terapéutico , Obesidad/prevención & control , Esquizofrenia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Benzodiazepinas/efectos adversos , Índice de Masa Corporal , Escalas de Valoración Psiquiátrica Breve , Método Doble Ciego , Graduación en Auxiliar de Enfermería , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/inducido químicamente , Olanzapina , Placebos , Aumento de Peso/efectos de los fármacosRESUMEN
En este trabajo se presenta el desarrollo de un método de cuantificación de ranitidina por cromatografía líquida en fase reversa, empleando como estándar interno un derivado suyo, la nizatidina. El método implica una etapa previa de purificación de las muestras utilizando para ello un sistema de extracción en fase sólida con columnas C18. Los extractos obtenidos se secan a 60ºC en un baño maría con corriente de nitrógeno. La cuantificación se lleva a cabo sobre una columna C8, con una fase móvil de fosfato de amonio pH 7.8 - metanol (70:30) a una velocidad de flujo de 1 mL/min y una longitud de onda de 322 nm. El procedimiento es objeto de validación y muestra ser lineal en un rango de 10.2 a 1600 ng/mL. Parámetros adicionales de validación, tales como: especificidad, precisión, exactitud y límite de cuantificación cumplen las especificaciones requeridas para este tipo de ensayos, conforme a la conferencia de Washington. La estabilidad de la ranitidina en plasma cuando las muestras se someten a ciclos de congelación y descongelación y a lo largo del periodo de almacenamiento también ha sido objeto de estudio
Asunto(s)
Ranitidina , Nizatidina , Cromatografía Líquida de Alta PresiónRESUMEN
El artículo proporciona información farmacológica sobre los medicamentos utilizados en el tratamiento de la úlcera péptica. Detalla también las características de los principios activos de las drogas utilizadas (AU)
Asunto(s)
Humanos , Úlcera Péptica , Antiulcerosos/farmacología , Úlcera Péptica/tratamiento farmacológico , Antiulcerosos/clasificación , Antiulcerosos/efectos adversos , Interacciones Farmacológicas , Antagonistas de los Receptores H2 de la Histamina/farmacología , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Cimetidina/farmacología , Cimetidina/uso terapéutico , Famotidina/farmacología , Famotidina/uso terapéutico , Nizatidina/farmacología , Nizatidina/uso terapéutico , Ranitidina/farmacología , Ranitidina/uso terapéuticoRESUMEN
El artículo proporciona información farmacológica sobre los medicamentos utilizados en el tratamiento de la úlcera péptica. Detalla también las características de los principios activos de las drogas utilizadas
Asunto(s)
Humanos , Antiulcerosos , Úlcera Péptica , Ranitidina , Famotidina , Cimetidina , Nizatidina , Interacciones Farmacológicas , Antagonistas de los Receptores H2 de la Histamina , Antiulcerosos , Úlcera Péptica/tratamiento farmacológicoRESUMEN
Helicobacter pylori (HP) infection is endemic worldwide. The proposed treatment is expensive and there are few reports regarding reinfection rates in Brazil. The aim of this study was to compare the eradication rates obtained with two therapeutic options and to evaluate reinfection one year after treatment. This was a prospective randomized trial with 55 patients. Thirty-nine patients had active duodenal ulcer (DU) and 16 non-ulcer dyspepsia (NUD), and all tested positive for HP. Diagnosis was based on at least two positive tests: ultrarapid urease test, histology and/or culture. Patients were randomized to two groups: group OMC treated with 40 mg omeprazole (once a day), 500 mg metronidazole and 250 mg clarithromycin (twice daily) for 7 days, or group NA treated with 300 mg nizatidine (once a day) and 1000 mg amoxicillin (twice daily) for 14 days. Those patients in whom HP was eradicated were followed up for one year to evaluate reinfection. Twenty-five patients were randomized for OMC and 30 for NA. HP eradication occurred in 20/25 patients (80 per cent) treated with OMC and 13/30 (43 per cent) treated with NA (P = 0.01). After reallocation because of initial treatment failure, the overall eradication rate was 44/51 patients (86 per cent). After an average follow-up of one year, we evaluated 34 patients (23 with DU and 11 with NUD). Reinfection occurred in 3/34 patients (7.6 per cent). We conclude that OMC is effective for HP eradication, and that NA should not be used. Reinfection occurs in 7.6 per cent of the patients in the first year after eradication.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Úlcera Duodenal/tratamiento farmacológico , Dispepsia/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Antiulcerosos/uso terapéutico , Claritromicina/uso terapéutico , Quimioterapia Combinada , Úlcera Duodenal/microbiología , Dispepsia/microbiología , Metronidazol/uso terapéutico , Nizatidina/uso terapéutico , Omeprazol/uso terapéutico , Penicilinas/uso terapéutico , Estudios Prospectivos , Recurrencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
The pharmacokinetics of oral ranitidine were studied in 24 Mexican male healthy volunteers. Subjects received a tablet containing 150 mg of ranitidine (Azantac TM, Glaxo de Mexico, Mexico, City) after an overnight fast and blood samples were drawn at several times for a period of 24 h. Ranitidine concentration in plasma was measured by high performance liquid chromatography and pharmacokinetic parameters were determined by non-compartmental analysis. Ranitide plasma concentration increased with time, reaching a maximum of (mean ñ SEM) 484 ñ 34 ng/ml in 2.7 ñ 0.2 h. Plasma levels then decayed with a terminal half-life of 4.8 ñ 0.3 h. The area under the plasma concentration against time curve was 2440 ñ 126 ngh/ml. Oral ranitidine pharmacokinetic parameters in mexicans appeared to be similar to those previously reported for caucasians
Asunto(s)
Adulto , Humanos , Masculino , Cromatografía , Cloruro de Metileno , Nizatidina , Farmacocinética , Plasma/efectos de los fármacos , Ranitidina/farmacocinéticaAsunto(s)
Humanos , Colinérgicos , Antiulcerosos , Antidiarreicos , Catárticos/clasificación , Ácido Gástrico , Ácidos Aminosalicílicos/farmacología , Cimetidina/química , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Antagonistas de Dopamina/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Inmunosupresores/farmacología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Nizatidina/efectos adversos , Ranitidina/químicaRESUMEN
A conformational study of two potent histamine H2-receptor antagonists, tiotidine and nizatidine, have been made. The geometry of cyanoguanidine and guanidinothiazol in tiotidine and diaminonitroetane in nizatidine was obtained using MNDO calculations. On the other hand, the conformations of the molecules, under study were obtained using a empirical atom-atom potential that stimulates the drug behavior in aqueous solution at 37 degrees C. For both molecules, folded and very rigid conformations, with a substantial parallelism between the planes of the rings and the polar groups, were obtained. All the possibilities of the configurational isomerism on the polar groups of this molecules was taken into account. The results obtained show that the polar group can adopt just staggered forms (Z,E and E,Z). These results agree with experimental and theoretical studies made on the polar group. The type of conformations found in tiotidine and nizatidine are very similar to those previously found for metiamide, cimetidine, ranitidine and etintidine. These results would permit us to propose that these conformations play a determinant role in the histamine H2-receptor recognition.
Asunto(s)
Cimetidina/química , Nizatidina/química , Receptores Histamínicos H2/química , Isomerismo , Modelos Teóricos , Conformación MolecularRESUMEN
Se realizó un estudio conformacional de dos potentes antagonistas en los receptores de H2 de histamina, tiodidina y nizatidina. Las geometrías de los grupos cianoguanidina y guanidinotiazol de tiotidina y el grupo diaminonitroetano de nizatidina fueron calculadas utilizando técnicas MNDO de la química cuántica. Mientras que las conformaciones de las moléculas en estudio se obtuvieron empleando un potencial átomo-átomo empírico que simula el comportamiento de las drogas en solución acuosa a 37-C. Para ambas moléculas se obtuvieron conformaciones plegadas, muy rígidas con un marcado paralelismo entre el plano de los anillos y el de los grupos polares. En las dos moleculas en estudio todas las posibilidades de isomerismo configuracional de los grupos polares fueron tenidas en cuenta: encontrándose que las únicas conformaciones posible son aquellas que tienen los grupos polares en la forma de los isómeros cruzados (Z-E o E-Z). Estos resultados están totalmente de acuerdo con los estudios experimentales y teóricos realizados en estos grupos polares. El tipo de conformaciones encontradas por totidina y nizatidina son muy similares a las encontradas previamente para metiamida, cimetidina, ranitidina y etintidina. Estos resultados nos permitirían proponer que este tipo de conformaciones juegan un rol determinante en el reconocimiento del receptor H2 de histamina