Estudio de bioequivalencia de montelukast en tabletas masticables de 5 mg / Bioequivalence study of montelukast 5 mg chewable tablets

Introducción. La importancia de los medicamentos genéricos radica en la posibilidad de la disminución de los costos en el sistema nacional de salud, sin sacrificar la calidad del servicio ni la eficacia y la seguridad de los tratamientos. Es importante resaltar que los estudios de bioequivalencia pretenden demostrar que los perfiles farmacocinéticos del producto de prueba y del producto de referencia son similares e intercambiables. El montelukast sódico está indicado para la profilaxis y el tratamiento crónico del asma, en adultos y pacientes pediátricos de 12 meses de edad o más. En general, es bien tolerado y las reacciones adversas son un poco más frecuentes en los pacientes tratados con el fármaco que en los tratados con placebo. Objetivos. Comparar la biodisponibilidad de Amisped®, montelukast en tabletas masticables de 5 mg fabricadas por Sanofi-Aventis con la de Singulair®, montelukast en tabletas masticables de 5 mg elaboradas por Merck Sharp & Dohme. Materiales y métodos. Se comparó la magnitud y la velocidad de la absorción de montelukast en 18 voluntarios sanos, empleando un diseño cruzado completo al azar. El bioanálisis de las muestras se hizo por cromatografía líquida de alta resolución. Resultados. Los resultados para el genérico y el innovador, respectivamente, fueron: Tmax (horas) 2,17±0,73 y 2,28±0,88; Cmax (ng/ml) 607,42±122,92 y 627,69±134,17; AUC0-t (ng*h/ml) 3.316,39±861,57 y 3.545,40±1.070,07; AUC0-∞ (ng*h/ml) 3.450,92±904,89 y 3.722,03±1120,60; Ke (1/h) 0,25±0,05 y 0,23±0,04 en el intervalo de confianza de 0,99-1,00 para lnCmax y 0,94-1,06 para lnAUC0-∞. Conclusiones. La formulación ensayada de Amisped® de Sanofi-Aventis es bioequivalente a la formulación de referencia Singulair® de Merck Sharp& Dohme.

Introduction. The importance of generic drugs is the possibility of reduced costs in the national health system without sacrificing quality of service and the efficacy and safety of treatments. However, bioequivalence studies must show that the pharmacokinetic profiles of the test product and reference product are similar and interchangeable. Montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months of age or older. It is generally well tolerated, although adverse reactions are more frequent in patients treated with the drug than in those treated with placebo. Objectives. To compare the bioavailability of Amisped® (5 mg montelukast chewable tablets) manufactured by Sanofi-Aventis and 5 mg chewable tablet montelukast (Singulair®) developed by Merck. Materials and methods. The magnitude and rate of absorption of montelukast was compared in 18 healthy volunteers using a randomized complete crossover design. The bioassay was performed by high performance liquid chromatography. Results. Results are indicated for the generic and innovator, respectively: Tmax (h) 2.17±0.73, 2.28±0.88; Cmax (ng/mL) 607.4±122.9, 627.7±134.2; AUC0-t (ng*h/ml) 3,316±861, 3,545±1,070; AUC0-∞ (ng*h/ml) 3,450±904, 3,722±1121; Ke (1/h) 0.25±0.05, 0.23±0.04 in the confidence range of 0.99-1.00 for lnCmax and 0.94-1.06 for lnAUC0-∞. Conclusions. The formula tested in Amisped® from Sanofi-Aventis is bioequivalent to the reference formulation of Merck Singulair®.

Efeito do buflomedil e da pentoxifilina, isolados ou em associação, na viabilidade de retalhos cutâneos dorsais de ratos submetidos previamente à administração de nicotina: estudo da viabilidade dos retalhos através do processamento digital das imagens obtidas / Effect of buflomedil and pentoxifylline, isolated or in association, on viability of dorsal skin flaps of rats previously submited to the nicotine administration: study of the viability of the flaps thru a digital process of the obtained images

Estudados 120 ratos da raça Wistar, divididos em oito grupos de 15 animais. Os animais foram submetidos à injeção dos fármacos buflomedil, pentoxifilina e nicotina. No sétimo dia de pós-operatório, o retalho dorsal foi fotografado, sua imagem digitalizada e transferida para o computador. Com o programa de imagem (Image Tool), a foto foi delineada e subdividida em cinco diferentes áreas: total, isquêmica, de necrose, de viabilidade e preservada. A obtenção dos valores percentuais das cinco diferentes áreas do retalho dorsal levou a uma maior compreensão da ação do buflomedil e da pentoxifilina na microcirculação do retalho, principalmente na área isquêmica / The study was conducted on 120 male Wistar rats, arranged in 8 groups of 15 animals each. The animals underwent a injection schedule of the following drugs: buflomedil, pentoxifylline and nicotine. At the end of the seventh post-op day, the dorsal flap was photographed, its image was digitalized and entered into a computer. With an image software (Image Tool) the photo was delineated and subdivided into five different segments: total, ischemic, necrotic, viability and preserved segments. The obtaining of the percentage values of the five different segments of the dorsal flap, allowed a better understanding of the action of buflomedil and pentoxifylline upon the microcirculation of the flap...