Farmacocinética de amicacina en ratones entrenados Translated title: Pharmacokinetics of amikacin administered in trained mice

Abstract

Los objetivos de este trabajo fueron determinar la bioquímica sanguínea y el comportamiento farmacocinético de amicacina en ratones con y sin entrenamiento físico. Se utilizaron 147 ratones sanos y con pesos de 25 a 35 g. Sesenta y un animales fueron asignados a la Experiencia 1 (E1) y 86 a la Experiencia 2 (E2). Los ratones de la E1 fueron entrenados nadando 20 minutos por día, 5 días a la semana durante 7 semanas. Los ratones de la E2 permanecieron sin entrenamiento. A 75 animales [n(E1) = 25 y n(E2) = 50] se les recolectó sangre para determinar la bioquímica sanguínea. A 72 animales [n(E1) = 36 y n(E2) = 36] se les administró amicacina (10 mg/kg) vía intramuscular y se tomaron muestras sanguíneas a tiempos controlados. Para los análisis cinético y estadístico se utilizaron un modelo no compartimental y ANOVA multifactorial, respectivamente. Los resultados bioquímicos se expresaron como (medias ± 1 DE): Se encontraron diferencias (P < 0,05) en los valores de creatina quinasa (1.266,9 ± 1181,3 y 66,0 ± 43,3 UI/L) y aspartato aminotransferasa (186,2 ± 23,8 y 150,1 ± 80,5 UI/L) de los ratones con y sin entrenamiento físico, respectivamente. Resultados farmacocinéticos (medias): Concentración máxima [Cmax (E1)] = 10,2 y (E2) = 14,8 µg/mL; tiempo en el que se logra la Cmax (E1 y E2) = 0,25 h; Constante de velocidad de eliminación (E1) = 0,31 y (E2) = 0,54 h-1 ; tiempo medio de eliminación (E1) = 2,2 y (E2) = 1,3 h y área bajo la curva (E1)= 13,9 y (E2) = 15,6 µg/mL/h. Las concentraciones de amicacina obtenidas durante la E1 y E2 no presentaron diferencias estadísticas (P > 0,05).

Translated abstract

The aim of the present paper was to determine the blood biochemistry and the pharmacokinetic behavior of amikacin administered to mice with and without physical training. One hundred and forty seven, adult male mice, weighing 25 to 35 gram b.w. were used. Sixty one animals were randomly assigned for Experience 1 (E1) and 86 for Experience 2 (E2). During E1, the mice were trained swimming 20 minutes a day 5 days a week during 7 weeks. E2 mice remained without training. Blood samples from 75 mice and [n(E1) = 25 and n(E2)= 50] were collected to determine the blood biochemistry. Seventy-two mice [n(E1)= 36 and n(E2)= 36] were administered with a single dose of amikacin by intramuscular route (10 mg/kg b.w.). One blood sample per animal (E1 and E2) was taken postadministration of the antibiotic. For kinetic and statistical analyses, non-compartment model and multifactorial ANOVA were used, respectively. The data for each time point was averaged and these values were used to calculate the pharmacokinetics parameters. Statistical differences (P< 0.05) were found in biochemical values (means ± 1 S.D) of creatine kinase (1,266.9 ± 1,181.3 and 66.0 ± 43.3 UI/L) and aspartate aminotransferase (186.2 ± 23.8 and 150.1 ± 80.5 UI/L) in mice with and without training, respectively. Results [Pharmacokinetic parameters (means)]: Maximum plasma concentration (E1) = 10.2 and (E2) = 14.8 µg/mL; time to reach maximum concentration (E1 and E2) = 0.25 h; smallest disposition rate constant (E1) = 0.31 and (E2) = 0.54 h-1; elimination half-life (E1) = 2.2 and (E2) = 1.3 h; area under the curve (E1) = 13.9 and (E2) = 15.6 µg/mL/h. Amikacin concentration-times obtained during E1 and E2 were not statistically different (P > 0.05).