Pharmacokinetics of methotrexate in children with acute lymphocytic leukemia.
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 (t1/2 beta) 3.0 +/- 0.7 h (mean +/- SD). The inter- and intrapatient 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 mumol/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 mumol/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.
Najjar
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Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyad, Saudi Arabia.
al Fawaz
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D002648:Child; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*
D008727:Methotrexate