Unpredictable serum levels after oral methotrexate in children with acute lymphoblastic leukaemia

Serum methotrexate levels were measured for 5 h after oral intake in 11 children with acute lymphoblastic leukaemia. The curves obtained with the child's regular dose of methotrexate varied widely, and were independent of the doses used. Peak levels were found in samples taken up to 3h after ingestion, and ranged from 300 to 1250 ng/ml. In the doses used, methotrexate toxicity was present in one of the eleven children, and was associated with a delayed peak and a high 5-h methotrexate level. Individual drug metabolism could be an important factor in the response to treatment, and needs to be evaluated in the assessment of protocols.