Accumulation of methotrexate in human tissues following high-dose methotrexate therapy

Methotrexate concentration was analyzed in a number of tissues of a patient of osteogenic sarcoma who had been on high-dose methotrexate therapy for nearly 6 months. Gall bladder and kidney contained the highest concentration of the drug, followed by testis, small intestine, skeletal muscle, bone marrow, lung, spleen, heart and liver. Although, compared to kidney the liver contained relatively small amount of the drug, yet nearly 1/5th of the total drug in liver was in bound form. This bound form of methotrexate is most likely associated with multiple forms of dihydrofolate reductase. The total concentration of methotrexate in kidney is 80 fold higher than the concentration of the drug in liver and 28 fold higher than the concentration in bone marrow. This suggests that in high-dose methotrexate therapy, nephrotoxicity is the more immediate threat to the patient than hepatotoxicity and bone marrow suppression.