Pharmacokinetics of Methotrexate and 7-Hydroxy-Methotrexate after High-Dose (33.6 g/m2) Methotrexate Therapy

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Abstract
We have measured MTX and 7-OH-MTX in plasma and urine samples from a 9-year-old boy treated with six consecutive 24-h IV high-dose MTX courses (33.6 g/m2) after a relapse of ALL. The between-course pharmacokinetics of MTX and 7-OH-MTX were found to be highly reproducible. Both MTX and 7-OH-MTX elimination followed a biphasic curve, initial half-lives (t1/2(α)) being 2.86 ± 0.44 h and 5.14 ± 0.46 h (mean ± SD) and second-phase biological half-lives (t1/2(β)) being approximately 18 and 16 h, respectively. The apparent volume of distribution for MTX was 0.8 L/kg, whereas the corresponding value for 7-OH-MTX was threefold less. Since clearance of MTX was within the range reported for lower doses, the data suggest that MTX pharmacokinetics are not dose-dependent up to 33.6 g/m.2

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