Neurotoxicity of benzylpenicillin: correlation to concentrations in serum, cerebrospinal fluid and brain tissue fluid in rabbits.
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.
Schliamser
S E
SE
Department of Infectious Diseases, University of Umeå, Sweden.
Bolander
H
H
Kourtopoulos
H
H
Norrby
S R
SR
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004569:Electroencephalography; D010400:Penicillin G / Q000097:blood / Q000134:cerebrospinal fluid / Q000633:toxicity*; D011817:Rabbits
D010400:Penicillin G