Inhibition of methotrexate transport from cerebrospinal fluid by probenecid.

In rabbit, the efflux of intraventricularly injected methotrexate from the cerebrospinal fluid was retarded by pretreatment with 200 mg/kg of ip probenecid. In vitro, the ability of the isolated choroid plexus to concentrate methotrexate was depressed by the inclusion of probenecid in the incubation medium. These experimental results are consistent with the hypothesis that probenecid depresses the clearance of methotrexate from the cerebrospinal fluid by blocking the transport of methotrexate from cerebrospinal fluid to blood via the choroid plexus.