Nakada Y, Yamamoto K, Kawakami J, Sawada Y, Iga T
Department of Pharmacy, University of Tokyo Hospital, Japan.
Pharm Res. 1995 Dec;12(12):1953-7. doi: 10.1023/a:1016200208174.
We investigated the effect of acute renal failure on the neurotoxicity of cimetidine in rats.
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.
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.
Increased sensitivity to the drug on the central nervous system may contribute to increased toxicity of cimetidine with renal failure.
我们研究了急性肾衰竭对大鼠西咪替丁神经毒性的影响。
通过双侧输尿管结扎制造实验性急性肾衰竭。将西咪替丁静脉输注到输尿管结扎（UL）大鼠和对照大鼠体内，并比较血浆、脑和脑脊液（CSF）中的西咪替丁浓度。
与对照大鼠相比，UL大鼠血浆中的西咪替丁浓度迅速升高。惊厥发作时脑脊液中的西咪替丁浓度不取决于输注速率，这表明脑脊液中的西咪替丁与阵挛性惊厥的作用部位迅速达到平衡。阵挛性惊厥发作时，UL大鼠脑脊液中的西咪替丁浓度低于对照大鼠。
对药物在中枢神经系统上的敏感性增加可能导致肾衰竭时西咪替丁毒性增加。
