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High dose methotrexate treatment in children with acute lymphoblastic leukaemia may be optimised by a weight-based dose calculation.

Jönsson, Peter LU ; Skärby, Tor LU ; Heldrup, Jesper LU ; Schrøder, Henrik and Höglund, Peter LU (2011) In Pediatric Blood & Cancer 57. p.41-46
Abstract
BACKGROUND: The inter-individual variation in exposure to methotrexate is considerable after intravenous high dose methotrexate (HDMTX) administration and both under- and over exposures may have dire consequences. Thus, optimal dose individualisation is of paramount importance. PROCEDURE: We studied how pharmacokinetic parameters were related to outcome in 340 patients with acute lymphoblastic leukaemia (ALL). A population pharmacokinetic model was developed with data from 1284 HDMTX courses in 304 children evaluating age, height, weight, body surface area (BSA), sex, serum creatinine and serum alanine aminotransferase as potential covariates. RESULT: Body weight improved the population pharmacokinetic model significantly more than any of... (More)
BACKGROUND: The inter-individual variation in exposure to methotrexate is considerable after intravenous high dose methotrexate (HDMTX) administration and both under- and over exposures may have dire consequences. Thus, optimal dose individualisation is of paramount importance. PROCEDURE: We studied how pharmacokinetic parameters were related to outcome in 340 patients with acute lymphoblastic leukaemia (ALL). A population pharmacokinetic model was developed with data from 1284 HDMTX courses in 304 children evaluating age, height, weight, body surface area (BSA), sex, serum creatinine and serum alanine aminotransferase as potential covariates. RESULT: Body weight improved the population pharmacokinetic model significantly more than any of the other patient characteristics, indicating that body weight may be the better way of dose normalisation. In a logistic regression analysis, higher values of clearance as well as volume of distribution were related to increased relapse risk in the standard (SR) and intermediate risk (IR) groups as well as in the entire cohort. A higher weight was strongly associated with worse outcome in the SR and IR groups, (P = 0.0186 and 0.0121, respectively). CONCLUSIONS: We conclude that dose normalisation of methotrexate according to body weigh may give more predictable pharmacokinetics of methotrexate and may also improve the outcome for children with ALL. Pediatr Blood Cancer © 2011 Wiley-Liss, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pediatric Blood & Cancer
volume
57
pages
41 - 46
publisher
John Wiley and Sons Inc.
external identifiers
  • wos:000290452400009
  • pmid:21425443
  • scopus:79955708418
ISSN
1545-5017
DOI
10.1002/pbc.22999
language
English
LU publication?
yes
id
2b296bca-6575-47c0-a985-9a1b4e0c6f10 (old id 1883644)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21425443?dopt=Abstract
date added to LUP
2011-04-01 17:30:25
date last changed
2017-01-01 07:34:27
@article{2b296bca-6575-47c0-a985-9a1b4e0c6f10,
  abstract     = {BACKGROUND: The inter-individual variation in exposure to methotrexate is considerable after intravenous high dose methotrexate (HDMTX) administration and both under- and over exposures may have dire consequences. Thus, optimal dose individualisation is of paramount importance. PROCEDURE: We studied how pharmacokinetic parameters were related to outcome in 340 patients with acute lymphoblastic leukaemia (ALL). A population pharmacokinetic model was developed with data from 1284 HDMTX courses in 304 children evaluating age, height, weight, body surface area (BSA), sex, serum creatinine and serum alanine aminotransferase as potential covariates. RESULT: Body weight improved the population pharmacokinetic model significantly more than any of the other patient characteristics, indicating that body weight may be the better way of dose normalisation. In a logistic regression analysis, higher values of clearance as well as volume of distribution were related to increased relapse risk in the standard (SR) and intermediate risk (IR) groups as well as in the entire cohort. A higher weight was strongly associated with worse outcome in the SR and IR groups, (P = 0.0186 and 0.0121, respectively). CONCLUSIONS: We conclude that dose normalisation of methotrexate according to body weigh may give more predictable pharmacokinetics of methotrexate and may also improve the outcome for children with ALL. Pediatr Blood Cancer © 2011 Wiley-Liss, Inc.},
  author       = {Jönsson, Peter and Skärby, Tor and Heldrup, Jesper and Schrøder, Henrik and Höglund, Peter},
  issn         = {1545-5017},
  language     = {eng},
  pages        = {41--46},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Pediatric Blood & Cancer},
  title        = {High dose methotrexate treatment in children with acute lymphoblastic leukaemia may be optimised by a weight-based dose calculation.},
  url          = {http://dx.doi.org/10.1002/pbc.22999},
  volume       = {57},
  year         = {2011},
}