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Vincristine in childhood leukaemia: no pharmacokinetic rationale for dose reduction in adolescents

Frost, BM; Lonnerholm, G; Koopmans, P; Abrahamsson, J; Behrendtz, M; Castor, Anders LU ; Forestier, E; Uges, DRA and de Graaf, SSN (2003) In Acta Pædiatrica 92(5). p.551-557
Abstract
Aim: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. Methods: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on day I of induction therapy. Plasma samples were drawn before and 10, 30, 360 and 1380 min after injection of vincristine 2.0 mg/m(2) (maximum dose 2.0 mg) and analysed by high-performance liquid chromatography. Results: The median value (and range) for distribution half-life was 6.4 min (0.8-11.8), elimination half-life 1014 min (258-2570), volume of distribution 445 L/m(2) (137-1241) and total body clearance 3 62 ml/min/m(2) (134-2553). No... (More)
Aim: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. Methods: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on day I of induction therapy. Plasma samples were drawn before and 10, 30, 360 and 1380 min after injection of vincristine 2.0 mg/m(2) (maximum dose 2.0 mg) and analysed by high-performance liquid chromatography. Results: The median value (and range) for distribution half-life was 6.4 min (0.8-11.8), elimination half-life 1014 min (258-2570), volume of distribution 445 L/m(2) (137-1241) and total body clearance 3 62 ml/min/m(2) (134-2553). No correlation was found between age and any of these pharmacokinetic parameters. The area under the concentration time curve (AUC) was significantly correlated to age (p = 0.002; rho - 0.31), as expected from the dosage of vincristine. The lower AUC in children with a body surface area >1 m(2), which is reached at 8-9 y of age, indicates that they received a less intense treatment because of the capping of the vincristine dose at 2.0 mg. Conclusions: Vincristine pharmacokinetics were not age dependent in this paediatric population. Thus, we found no pharmacokinetic rationale for dose reduction in adolescents. The common practice of limiting the vincristine dose to 2.0 mg should be carefully reconsidered. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
vincristine, pharmacokinetics, acute lymphoblastic leukaemia, children
in
Acta Pædiatrica
volume
92
issue
5
pages
551 - 557
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • pmid:12839283
  • wos:000183542300007
  • scopus:10744227496
ISSN
1651-2227
DOI
language
English
LU publication?
yes
id
eb698b7b-2260-4653-ae70-94a7e8070e8d (old id 308760)
date added to LUP
2007-09-03 09:26:53
date last changed
2018-05-29 10:19:46
@article{eb698b7b-2260-4653-ae70-94a7e8070e8d,
  abstract     = {Aim: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. Methods: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on day I of induction therapy. Plasma samples were drawn before and 10, 30, 360 and 1380 min after injection of vincristine 2.0 mg/m(2) (maximum dose 2.0 mg) and analysed by high-performance liquid chromatography. Results: The median value (and range) for distribution half-life was 6.4 min (0.8-11.8), elimination half-life 1014 min (258-2570), volume of distribution 445 L/m(2) (137-1241) and total body clearance 3 62 ml/min/m(2) (134-2553). No correlation was found between age and any of these pharmacokinetic parameters. The area under the concentration time curve (AUC) was significantly correlated to age (p = 0.002; rho - 0.31), as expected from the dosage of vincristine. The lower AUC in children with a body surface area >1 m(2), which is reached at 8-9 y of age, indicates that they received a less intense treatment because of the capping of the vincristine dose at 2.0 mg. Conclusions: Vincristine pharmacokinetics were not age dependent in this paediatric population. Thus, we found no pharmacokinetic rationale for dose reduction in adolescents. The common practice of limiting the vincristine dose to 2.0 mg should be carefully reconsidered.},
  author       = {Frost, BM and Lonnerholm, G and Koopmans, P and Abrahamsson, J and Behrendtz, M and Castor, Anders and Forestier, E and Uges, DRA and de Graaf, SSN},
  issn         = {1651-2227},
  keyword      = {vincristine,pharmacokinetics,acute lymphoblastic leukaemia,children},
  language     = {eng},
  number       = {5},
  pages        = {551--557},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Acta Pædiatrica},
  title        = {Vincristine in childhood leukaemia: no pharmacokinetic rationale for dose reduction in adolescents},
  url          = {http://dx.doi.org/},
  volume       = {92},
  year         = {2003},
}