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Pharmacokinetics of methotrexate in infants with acute lymphoblastic leukemia
Author(s) -
Thompson P.,
Dreyer Z. E.,
Blaney S.,
Berg S.,
Murry D.,
Bomgaars L.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.176
Subject(s) - cmax , pharmacokinetics , methotrexate , medicine , dosing , antifolate , clinical pharmacology , lymphoblastic leukemia , pharmacology , acute lymphocytic leukemia , gastroenterology , pediatrics , antimetabolite , leukemia
An understanding of methotrexate (MTX) pharmacokinetics (PK) is important to achieve drug dosing that optimizes efficacy and minimizes toxicity. Limited information is available on the PK behavior of MTX in infants. Objectives To determine the PK of MTX and 7‐OH MTX in infants, and to compare the PK parameters of infants to those in older children. Methods A subset of patients enrolled on the POG 9407 infant leukemia study participated in this MTX PK study. MTX (4 mg/m 2 ) was administered i.v. over 24 h on week 4, day 22 of treatment. Sixteen patients, median age 7.8 months (range, 4–13 months) had blood samples collected for analysis of MTX concentrations at 1, 6, 12, and 23 h after the start of the infusion. MTX concentrations were also measured as part of standard clinical practice at the end of the infusion and every 24 h until the MTX level was < 0.18 μM. Model independent PK parameters (AUC, C max ) were determined for each patient. MTX PK data were also analyzed using a two‐compartment/first order model (ADAPT). Results: (See Table) Conclusions The estimated MTX CL for infants >3 months of age was very similar to that reported for older children between 1‐19 years of age (103–151 ml/min/m 2 ). Further study of MTX PK in infants <3 months is ongoing. Clinical Pharmacology & Therapeutics (2004) 75 , P47–P47; doi: 10.1016/j.clpt.2003.11.176MTX 7‐0H MTXAUC (μM‐hr) 1750 ± 400 255 ± 128 C max (μM) 58 ± 17 9.3 ± 4.5 CL (ml/min/m 2 ) 116 ± 30 ‐ V c (L/m 2 ) 14.6 ± 4.6 ‐ V p (L/m 2 ) 6.9 ± 6.3 ‐ t 1/2 distribution (h) 1.4 ± 0.63 ‐ t 1/2 elimination (h) 7.7 ± 4.9 ‐