- Shunsuke Kobayashi: Dept. of Pharmacy, The Institute of Medical Science Hospital, The University of Tokyo.
High-dose methotrexate therapy(HDMTX)is effective against lymphoid malignancies. However, delayed elimination of methotrexate(MTX)after HDMTX administration may lead to severe adverse drug reactions. We surveyed the drugs coadministered with MTX and the incidence of delayed MTX elimination in patients treated with HDMTX in a clinical setting. We analyzed the plasma MTX concentration in 110 samples after 55 cycles of HDMTX in 33 patients. Delayed MTX elimination was defined as a plasma MTX concentration ≥1.0 mmol/L at 48 h after the start of HDMTX administration or ≥0.1 mmol/L at 72 h after the start of HDMTX administration. The incidence of the combined use of drugs affecting MTX excretion and drugs that exhibited typical renal excretion was 84.8%(n=28). The incidence of delayed MTX elimination was 39.4%(n=13). MTX-induced acute kidney injury occurred in 9 patients, all of whom also exhibited delayed MTX elimination. Therefore, when prescribing HDMTX, it is important to monitor adverse events, including acute kidney injury, which may be induced by prolonged MTX blood concentrations.