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. G entamicin (3 mg/kg, iv) was administered 24 hours after an endotoxin c hallenge (5 mg/kg, ip). Some blood biochemical parameters, viz. urea, AST, GGT activities in addition to PCV and Hb concentration and creati nine clearance were also measured. In young animals, endotoxin caused prolongation in gentamicin half life (t(1/2)), increased area under th e plasma concentration-time curve (AUG) and reduced total body clearan ce (ClB) and volume of distribution (Vd). Endotoxin effects in the old rats were qualitatively similar to those induced in the young but wer e more pronounced. They included more than 10 fold increase in the t(1 /2) and AUG. In addition, a rising early phase in gentamicin plasma co ncentration was noticed in old rats treated with endotoxin which was, probably, due to an early redistribution process of gentamicin. The re sults indicate that aging and endotoxin, individually, can significant ly alter gentamicin pharmacokinetics in the rat. These alterations wer e exacerbated when endotoxemia was induced in old rats.