The effect of endotoxin on tobramycin pharmacokinetics in young and aged rats

The pharmacokinetics of tobramycin as a single intravenous dose (3 mg/kg) were determined in young (2-3 months) and aged (22-24 months) rats and in similar groups 24 h after a single intraperitoneal injection of endotoxin (5 mg/kg). In aged rats the systemic clearance of tobramycin was significantly lower than in young rats. Endotoxin significantly decreased tobramycin clearances in both age groups, the effect being more pronounced in aged rats. The endogenous creatinine clearance followed a similar pattern as the tobramycin clearance. The volume of distribution at steady state (Vdss) was significantly lower in aged rates than in young rats. Endotoxin tended to increase Vdss in both age groups. In aged rats, however, Vdss was still significantly lower than values from young rats. The mean residence time (MRT) and terminal half-life (t1/2 beta) of tobramycin were similar in young and aged rats. Endotoxin had no effect on these parameters in young rats when compared with their controls. In aged rats, however, endotoxin significantly prolonged both MRT and t1/2 beta when compared with normal aged rats and with young endotoxin-treated rats.