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 produced by bilateral ureteral ligation. ENX was intravenously infused to ureter 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. Brain/plasma concentration ratio (Kp)-time profile of ENX was similar in UL and control rats. Brain concentration of ENX at the occurrence of convulsion did not depend on the infusion rate, suggesting that in the brain tissue it equilibrates rapidly with the site of action for clonic convulsion. Brain concentration of ENX in UL rats at the occurrence 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 caused by not only decreased capability for renal elimination of ENX but also increased sensitivity to convulsant activity of ENX in the central nervous system.
Kawakami
J
J
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo, Japan.
Ohashi
K
K
Yamamoto
K
K
Sawada
Y
Y
Iga
T
T
D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000633:toxicity; D003292:Convulsants / Q000633:toxicity; D015365:Enoxacin / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
D000890:Anti-Infective Agents; D003292:Convulsants; D015365:Enoxacin; D002939:Ciprofloxacin