Effects of probenecid on methotrexate exchange between the blood and the cerebrospinal fluid.
In rabbits anesthetized with urethane, only a small fraction of 3H-methotrexate administered by an i.v. infusion reached an artificial cerebrospinal fluid solution perfused through the cerebroventricular system. This movement was not altered significantly by probenecid administered either i.v. or in the perfusing artificial cerebrospinal fluid. When the 3H-methotrexate was perfused through the cerebroventricular system, one third of the amount normally lost during the perfusion was retained when probenecid was also added to the solution. Therefore, at least a portion of the apparent blood-brain barrier that exists for methotrexate is due to removal from the cerebrospinal fluid by a process that can be inhibited by probenecid.
D000818:Animals; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D008727:Methotrexate / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D010477:Perfusion; D011339:Probenecid / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors
D011339:Probenecid; D008727:Methotrexate