Abstract

RULE, Roberto; VITA, Mariangeles; BASCHAR, Hugo  and  FARINA, Osvaldo Hugo. Pharmacokinetics and penetration into tissue fluid of cefepime administered to hyperthermic rabbits. Acta bioquím. clín. latinoam. [online]. 2008, vol.42, n.2, pp.221-225. ISSN 0325-2957.

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 [C_max (E1 LT)=23.5±3.4 and (E2 LT)=27.6±3.6 (µg/mL]; time to reach C_max [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.

Keywords : Kinetics; Cefepime; Lipopolysacharide; Tissue cage fluid; Rabbits.

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