Pharmacokinetics of methotrexate given intrathecally to children with acute lymphoblastic leukemia.

Pharmacokinetics of the intrathecally given methotrexate (MTX) for protection of the central nervous system was studied in 17 children with acute lymphoblastic leukemia (ALL). MTX plasma levels were assayed by enzymatic inhibition. The first order rate constants for the absorption, distribution and elimination phases were calculated on the base of an open one or two compartment body model. The efflux of MTX from the cerebrospinal fluid compartment is sufficiently significant to worsen myelosuppression, especially in 3-7 year old children. Therefore MTX cannot be administered intrathecally to such young children unless the complete remission in the number of circulating granulocytes is achieved according to general rules.