The effects of irradiation and probenecid on cerebrospinal fluid transport of penicillin.

A hitherto unrecognized interaction between whole brain irradiation and probenecid on cerebrospinal fluid (CSF) transport of benzylpenicillin has been demonstrated in rabbits. Healthy adult rabbits received 10 Gy (1000 rad) to the whole brain as a single dose. At different time intervals after irradiation the animals were subjected to single intravenous injections of benzylpenicillin. Studies on benzylpenicillin concentrations in CSF showed increasing values one week after irradiation suggesting disturbance in blood-CSF barriers. Additionally, groups of rabbits were subjected to either irradiation, probenecid injections or both prior to antibiotic administration. All these treatments resulted in increased CSF concentration of benzylpenicillin relative to the concurrent serum levels. The increase of the CSF benzylpenicillin levels in the preirradiated animals was less pronounced in the animals treated with probenecid, compared to those who were irradiated only. The mode by which probenecid and irradiation interacts on the CSF kinetics of benzylpenicillin should be further evaluated.