Plasma methotrexate (MTX) levels were measured in 10 children (age 3-12 years) who received a total of 43 infusions of MTX. The total dose (1,000 mg/m2) was administered as a bolus of 200 mg/m2 with 24-hour infusions of 800 mg/m2. The clearance was fast at 158 ± 81 ml/min/m2 and the elimination half-life (t½β) 3.0 ± 0.7 h (mean ± SD). The inter- and intrapa-tient variations in the steady state were wide, up to 6 times, suggesting the need for dose adjustment during infusion. The patients were at low risk for toxicity with a predicted MTX concentration at 39 h (5 half-lives) postinfusion of 0.28 ± 0.10 p:mol/l (mean ± SD). None of them required leucovorin rescue 72 h postinfusion. An additional assessment of the MTX level may be useful as a guide to the duration of leucovorin rescue, which may be more or less than the routine 72 h postinfusion. The time suggested for this assessment was 48 h postinfusion. The mean ± SD concentration at this time was 0.23 ± 0.12 μmol/l and it correlated (r = 0.841) with the level measured 36 h postinfusion (n = 10). The value of this level needs to be investigated on a larger number of infusions.

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