Effect of endotoxin on gentamicin pharmacokinetics in old and young adult rats

The effect of endotoxin administration on gentamicin pharmacokinetics in young adult (2-3 months) and old (22-24 months) rats was studied. Gentamicin (3 mg/kg, iv) was administered 24 hours after an endotoxin challenge (5 mg/kg, ip). Some blood biochemical parameters, viz. urea, AST, GGT activities in addition to PCV and Hb concentration and creatinine clearance were also measured. In young animals, endotoxin caused prolongation in gentamicin half life (t1/2), increased area under the plasma concentration-time curve (AUC) and reduced total body clearance (ClB) and volume of distribution (Vd). Endotoxin effects in the old rats were qualitatively similar to those induced in the young but were more pronounced. They included more than 10 fold increase in the t1/2 and AUC. In addition, a rising early phase in gentamicin plasma concentration was noticed in old rats treated with endotoxin which was, probably, due to an early redistribution process of gentamicin. The results indicate that aging and endotoxin, individually, can significantly alter gentamicin pharmacokinetics in the rat. These alterations were exacerbated when endotoxemia was induced in old rats.