Effect of renal failure on neurotoxicity of ranitidine in rats.
We investigated the effect of acute renal failure on the neurotoxicity of ranitidine in rats. Experimental acute renal failure was produced by bilateral ureteral ligation. Ranitidine was infused into the ureter ligated (UL) and control rats at the rate of 3.25 mg/min through the jugular vein until the onset of clonic convulsion. In UL rats, the onset time of convulsion was shorter and ranitidine concentrations in plasma and cerebrospinal fluid (CSF) were lower than those of control rats. However, the ranitidine concentration in the brain at the onset of convulsion was not different between the UL and control rats. From these findings, we concluded that acute renal failure is one of the risk factors for ranitidine neurotoxicity, and the increased sensitivity to the drug on the central nervous system may contribute to the increased toxicity of ranitidine in renal failure.
Nakada
Y
Y
Department of Pharmacy, University of Tokyo Hospital, Japan.
Yamamoto
K
K
Kawakami
J
J
Sawada
Y
Y
Iga
T
T
D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D006635:Histamine H2 Antagonists / Q000633:toxicity*; D008297:Male; D011899:Ranitidine / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced
D006635:Histamine H2 Antagonists; D011899:Ranitidine