Farmacocinética y penetración en líquido tisular de cefepime administrado en conejos hipertérmicos / Pharmacokinetics and penetration into tissue fluid of cefepime administered to hyperthermic rabbits

RESUMEN

La farmacocinética sérica y tisular de cefepime administrado por vía endovenosa (20 mg/kg de peso) fue determinada en conejos sanos, con hipertermia producida por lipopolisacáridos de E. coli e implantados en tejido subcutáneo con cajas para recolección de líquido tisular. Diez conejos adultos fueron utilizados en dos experiencias (E1 y E2). Las concentraciones de cefepime en suero (S) y líquido tisular (LT) fueron determinadas por método biológico. Para el análisis cinético se utilizó un modelo no compartimental. Los resultados farmacocinéticos (medias ± error estándar) fueron tiempo medio de eliminación [t1/2 (E1 S)=1,5±0,2 y (E2 S)=2,0±0,2 h] (p<0,05), área bajo la curva [ABC (E1 S)=181,6±17,5 y (E2 S)=192,3±18,5 (µg/mL/h]; Volumen de distribución en estado estacionario [Vss (E1S)=0,31±0,05 y (E2 S)=0,69±0,28 L/kg] (p<0,05); aclaramiento sérico [CL(E1 S)=118,3±17,7 y (E2 S) =93,1±19,9 (mL/h)kg] (p<0,05); Concentración máxima [Cmax (E1 LT)= 23,5±3,4 y (E2 LT)= 27,6±3,6 (µg/mL]; tiempo en el que se logra la Cmax [t max (E1 LT)=2,3±0,4 y (E2 LT)=1,7±0,4 h)]; t1/2 (E1 LT)= 2,4±0,3 y (E2 LT)=3,4±0,3 h (p<0,05); ABC (E1 LT)=122,0±12,7 y (E2 LT)=156,9±13,6 (µg/mL/h). y penetración [P (E1 LT)=67,3±8,7 y (E2 LT)=88,5±8,7%].

ABSTRACT

The pharmacokinetic characteristics in serum and tissue of cefepime given intravenously (20 mg/kg body weight) were assessed in healthy rabbits and in rabbits with hyperthermia induced by lipopolysacharide of E. coli, with tissue fluid cages implanted subcutaneously. Ten adult rabbits were used in two trials (E1 and E2). Cefepime concentrations in serum (S) and tissue cage fluid (LT) were determined by biological methods. The kinetic analysis was performed by means of a noncompartmental model. Pharmacokinetic results (means ± standard error) half life of elimination [t1/2 (E1 S)=1.5±0.2 and (E2 S)=2.0±0.2 h] (p<0.05), area under the curve [ABC (E1 S)=181.6±17.5 and (E2 S)= 192.3±18.5 (µg/mL/h]; volume of distribution at steady-state [Vss (E1 S)=0.31±0.05 and (E2 S)=0.69±0.28 L/kg] (p<0.05); total serum clearance [CL (E1 S)=118.3±17.7 and (E2 S)=93.1±19.9 (mL/h)kg] (p<0.05); maximum concentration [Cmax (E1 LT)=23.5±3.4 and (E2 LT)=27.6±3.6 (µg/mL]; time to reach Cmax [t max (E1 LT) =2.3±0.4 and (E2 LT)=1.7±0.4 h)]; t1/2 (E1 LT)=2.4±0.3 and (E2 LT)=3.4±0.3 h (p<0.05); ABC (E1 LT)=122.0±12.7 and (E2 LT)=156.9±13.6 (µg/mL/h); penetration [P (E1 LT)=67.3±8.7 and (E2 LT)=88.5±8.7%]. In conclusion, the pharmacokinetic changes of cefepime observed in rabbits with hyperthermia induced by lipopolysacharide, could be clinically significant if not taken into account when designing the dosing regimens.