Relative pharmacokinetics of three amikacin brands in onco-hemotologic pediatric patients experiencing febrile neutropeina

Abstract

Three commercially available brands of amikacin were investigated in a parallel study design for the assessment of comparative pharmacokinetics in pediatric oncology patients with chemotherapy-induced neutropenic febrile episode. Amikacin concentration in serum samples was determined by fluorescence polarization immunoassay method using Abbott TDx system. Computer software, PK II was used for computation of pharmacokinetic parameters of amikacin. The serum concentration of all brands nonsignificantly (p > 0.05) varied at all time points, except at 1 and 2 hrs post dosing. At 1 hr post dosing, the serum concentration of brand II varied from rest of two brands. Whereas at 2 hr following I/V infusion, brands II and I were statistically different. Highest serum concentration of 38.69 +/- 1.45 microg/ml was observed in case of brand III while brands I and II showed lower but not significantly different serum concentration values, i.e., 36.30 +/- 1.65 and 37.89 +/- 1.32 microg/ml, respectively when compared with brand I. The other pharmacokinetic parameters of 3 brands found to have non-significant difference (P < 0.05) except, t(1/2)alpha and Cl of brands I and II that deviated statistically significant (p < 0.01). The relative bioavailability of brand II and III as compared with brand I, considered as standard 86.17 and 96.86%, respectively falls within the accepted limits of +/- 20% required for the bioequivalence of any two brands. Based upon findings of the present study, all these brands may be used interchangeably in oncology patients. Further studies, however are needed to determine whether the statistically elevated Cl value in brand II is of any clinical significance.

Monitorización terapéutica de antimicrobianos en pediatría. Revisión de la experiencia latinoamericana

“…Dentro de sus características se destaca un efecto bactericida rápido y sinergia cuando se usa junto a b-lactámicos 18,19 . Su mecanismo de acción tiene dos fases, la primera de efecto bactericida rápido, que depende de la concentración máxima, y la segunda fase de efecto bactericida lento, que es independiente de la concentración del fármaco, y conocida como efecto post antibiótico, base para recomendar su uso como monodosis diaria [20][21][22][23] . El uso de monodosis de amikacina en el tratamiento de neutropenia febril en adultos y niños es reconocido en la literatura médica [27][28][29] (Tabla 3), habiéndose demostrado su eficacia clínica y microbiológica.…”

“…Tréluyer y cols., analizaron el uso de dosis únicas y múltiples diarias de amikacina en 155 neonatos, lactantes y niños a través de monitorización farmacocinética, recomendando el uso de monodosis en todas las edades y una Cmáx superior a la CIM por un factor de al menos 8, con una concentración basal menor que 1 μg/mL [21][22][23][24][25][26][27][28][29] .…”

SomeIn Vitro/In VivoChemically-Induced Experimental Models of Liver Oxidative Stress in Rats

“…In vitro experiments are carried out in primary isolated rat hepatocytes [13] or liver microsomes [14]. Cell incubation with CCl 4 (86  μ mol L −1 ) leads to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH, and elevation in MDA quantity.…”

“…For in vivo experiments Wistar rats are challenged with a single dose (2 mL/kg) of 20% of CCl 4 in olive oil [15]. These in vitro/in vivo CCl 4 -induced liver injury models are useful for investigations on hepatoprotective and antioxidant properties of some plant-derived biologically active compounds [13–17]. …”