Figure 3.

Pharmacokinetically guided leucovorin rescue based on plasma MTX levels after high-dose MTX. Leucovorin dosing must be increased dramatically when plasma MTX levels are elevated above 5 µM at 42 hours after the start of the MTX infusion because leucovorin must compete with MTX to enter cells via the reduced folate carrier and the goal of leucovorin rescue is to achieve a high intracellular concentration of leucovorin. In color are the recommended doses of leucovorin based on the plasma MTX concentration at each time point after the start of the MTX infusion. For example, if at hour 60 the MTX concentration is 100 µM, it falls above the red line and the recommended leucovorin dose would be 1,000 mg/m² every 6 hours. If at 100 hours the methotrexate concentration decreases to 3 µM (above the yellow line, below the orange line), then the recommended leucovorin dose would decrease to 10 mg/m² every 3 hours. The dotted lines indicate extrapolated values based on modeling and clinical trial experience following the original publication [113].

Abbreviation: MTX, methotrexate.