Schliamser S E, Bolander H, Kourtopoulos H, Norrby S R
Department of Infectious Diseases, University of Umeå, Sweden.
J Antimicrob Chemother. 1988 Mar;21(3):365-72. doi: 10.1093/jac/21.3.365.
The neurotoxic potential of benzylpenicillin, administered as continuous intravenous infusion, was studied in rabbits. Thirteen animals were killed at the onset of epileptogenic EEG activity (seven) or convulsions (six). Benzylpenicillin levels were determined in serum, cerebrospinal fluid (CSF) and brain tissue fluid. High doses of benzylpenicillin were required to induce neurotoxicity; epileptogenic (EEG) changes were seen at serum levels of 510-960 mg/l and convulsions at 920-1902 mg/l. Neurotoxicity correlated well with levels of benzylpenicillin in brain tissue fluid, calculated as 10 x the concentration in whole brain tissue. The correlation of neurotoxic reactions to levels of benzylpenicillin in CSF was poor and the CSF levels were consistently lower than those in brain tissue fluid. The technique used was found to be a satisfactory, though laborious, way to study neurotoxicity of drugs.
通过持续静脉输注给予苄青霉素，研究其对家兔的神经毒性潜力。在癫痫性脑电图活动开始时（7只）或惊厥发作时（6只）处死13只动物。测定血清、脑脊液（CSF）和脑组织液中的苄青霉素水平。诱导神经毒性需要高剂量的苄青霉素；血清水平为510 - 960mg/L时出现癫痫性（脑电图）变化，920 - 1902mg/L时出现惊厥。神经毒性与脑组织液中苄青霉素水平密切相关，计算方法为全脑组织浓度的10倍。神经毒性反应与脑脊液中苄青霉素水平的相关性较差，且脑脊液水平始终低于脑组织液中的水平。发现所采用的技术是研究药物神经毒性的一种令人满意但费力的方法。
