Vincristine can its therapeutic index be enhanced

Since vincristine plays a key role in the treatment of childhood acute lymphoblastic leukaemia ALL , it is worthwhile to explore if efficacy can be improved by individual dose adjustment.

Therefore, we studied the relationship between vincristine antileukaemic effect and pharmacokinetics in children newly diagnosed with ALL before the start of standard induction chemotherapy. Vincristine plasma concentration was measured by high-pressure liquid chromatography analysis with electrochemical detection. Primary pharmacokinetic parameters were estimated by maximum a posteriori parameter estimation with a Bayesian algorithm using the ADAPT II software package.

Secondary pharmacokinetic parameters were calculated from the model. Response to a single dose of vincristine was determined on bone marrow BM and peripheral blood PB smears after 3 days. Variability of vincristine pharmacokinetics did not explain variability of response to vincristine monotherapy. Our results do not support the clinical application of pharmacokinetically guided adaptation of a standard body surface area-based dose of vincristine. The use of hematopoietic stem cell transplantation or blood and marrow transplantation bmt is on the increase worldwide.

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Download references. We thank the Laboratory of Systems Pharmacology at Harvard Medical School and the Boone lab at University of Toronto for providing access to their equipment for experiments, the Cowen lab for providing GFP- albicans , the Springer lab for providing mCherry- cerevisiae.

We thank Michael Baym, Remy Chait, and Roy Kishony for providing access and support in use of fluorescence photography. The authors would like to thank Susan E Leeman for critical discussion of the manuscript. You can also search for this author in PubMed Google Scholar. Correspondence to Murat Cokol.

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