Methotrexate cerebrospinal fluid pharmacokinetics in a patient with lymphoma treated with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone.
The role of "moderate-dose" systemic methotrexate in preventing central nervous system lymphomatous relapse is unknown. Certain patients with diffuse non-Hodgkin's histologic subtypes have an increased risk of relapse in the central nervous system, and it would be helpful to know if intravenous "moderate-dose" methotrexate might treat or possibly protect the meninges from involvement. In part, the rationale behind the recent regimen of methotrexate, bleomycin, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), and dexamethasone (m-BACOD) is to protect the central nervous system, and the empiric proof of this protection awaits the follow-up results of trials currently underway. In the meantime, the systemic and cerebrospinal fluid pharmacokinetics of moderate-dose intravenous methotrexate were studied in one patient whose histologic subtype places him at high risk for central nervous system involvement. Although the central nervous system levels of methotrexate in this patient never reached 1 X 10(-6) M, the levels exceeded 1 X 10(-7) M for at least 24 hours. The implications of peak dose versus sustained exposure to a lower dose of methotrexate are discussed.
D000971:Antineoplastic Combined Chemotherapy Protocols; D001761:Bleomycin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D007700:Kinetics; D002955:Leucovorin / Q000008:administration & dosage; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D008875:Middle Aged; D014750:Vincristine / Q000008:administration & dosage
D001761:Bleomycin; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D002955:Leucovorin; D008727:Methotrexate