EFFECT OF ACUTE-RENAL-FAILURE ON NEUROTOXICITY OF ENOXACIN IN RATS

We investigated the effect of acute renal failure on the neurotoxicity of enoxacin (ENX) in rats. Experimental acute renal failure was produ ced by bilateral ureteral ligation, ENX was intravenously infused to u reter ligated (UL) and control rats, and its concentration in plasma, brain and cerebrospinal fluid (CSF) was compared, Plasma concentration of ENX increased rapidly in UL rats as compared with control rats. Br ain/plasma concentration ratio (K-p)-time profile of ENX was similar i n UL and control rats. Brain concentration of ENX at the occurrence of convulsion did not depend on the infusion rate, suggesting that in th e brain tissue it equilibrates rapidly with the site of action for clo nic convulsion. Brain concentration of ENX in UL rats at the occurrenc e of clonic convulsion was lower than that in control rats. A similar tendency was also observed with CSF concentration. In conclusion, the potentiation of neurotoxicity of ENX with acute renal failure may be c aused by not only decreased capability for renal elimination of ENX bu t also increased sensitivity to convulsant activity of ENX in the cent ral nervous system.