Methotrexate concentration in cerebrospinal fluid of the space created by tumor removal

This paper investigates the post-surgical pharmacokinetics of methotrexate (MTX) in the plasma, the cerebrospinal fluids (CSF), and the spaces created by tumor removal (STR) in patients with glioblastoma, during hyperosmotic disruption of the blood brain barrier (HODBBB) and intra-arterial chemother apy with MTX. Eight Japanese patients with glioblastoma, three with open ST Rs and five with closed STRs, received a total of thirteen courses of HODBB B and intra-arterial combination chemotherapy: with MTX. The patients were initially administered mannitol, then the anticancer drugs were infused int o the carotid artery. Samples of blood and CSF from the STRs were obtained. MTX concentrations were measured by fluorescence polarization immunoassay and the pharmacokinetic parameters of MTX in plasma and CSF were estimated. The plasma concentrations of MTX peaked at the end of drug infusion, and t hen decayed bi-exponentially during the remainder of the treatment period. The CSF concentration of MTX in the STR peaked 2 h after drug administratio n, then mono-exponentially decreased. The area under the concentration time curve (AUC) for plasma and CSF MTX concentrations increased in parallel wi th the MTX dose. In patients with open STRs, the mean AUC of MTX in CSF was 4.44% of that found in plasma, while in patients with closed STRs, the mea n was 61.2% of that found in plasma. In the latter group, the MTX administe red using HODBBB and intra-arterial chemotherapy was maintained in the STRs for long periods.