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Effect of acute renal failure on neurotoxicity of cimetidine in rats
Y Nakada1, K Yamamoto, J Kawakami
1Department of Pharmacy, University of Tokyo Hospital, Japan.
Purpose:
We investigated the effect of acute renal failure on the neurotoxicity of cimetidine in rats.
Methods:
Experimental acute renal failure was produced by bilateral ureteral ligation. Cimetidine was intravenously infused to ureter ligated (UL) and control rats, and cimetidine concentration in plasma, brain and cerebrospinal fluid (CSF) were compared.
Results:
The cimetidine concentration in plasma was rapidly increased in UL rats as compared to control rats. The cimetidine concentration in CSF at the onset of convulsion did not depend on the infusion rate, suggesting that cimetidine in CSF equilibrates rapidly with the site of action for clonic convulsion. The cimetidine concentration in CSF of UL rats at the onset of clonic convulsion was lower than those of control rats.
Conclusions:
Increased sensitivity to the drug on the central nervous system may contribute to increased toxicity of cimetidine with renal failure.