Slower degradation rate of cytarabine in blood samples from acute myeloid leukemia by comparison with control samples
Purpose Cytarabine, a key chemotherapy agent for acute myeloid leukemia (AML) treatment, is deaminated into inactive uracil-arabinoside by cytidine deaminase. This deamination leads to samples stability issues with respect to clinical pharmacokinetic trials. The aim of our study was to study in vitr...
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Published in | Cancer chemotherapy and pharmacology Vol. 86; no. 5; pp. 687 - 691 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.11.2020
Springer Verlag |
Subjects | |
Online Access | Get full text |
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Summary: | Purpose
Cytarabine, a key chemotherapy agent for acute myeloid leukemia (AML) treatment, is deaminated into inactive uracil-arabinoside by cytidine deaminase. This deamination leads to samples stability issues with respect to clinical pharmacokinetic trials. The aim of our study was to study in vitro cytarabine stability in blood samples obtained from AML patients.
Methods
Cytarabine quantification was performed using a fully validated LC/MS/MS method. In vitro cytarabine stability was assessed at room temperature over 24 h in samples coming from 14 AML patients and 7 control patients (CTRL) with no hematological malignancy. In vitro concentrations versus time data were analyzed using a noncompartmental approach.
Results
Cytarabine in vitro area under the curve (AUC
IVlast
) was 22-fold higher in AML samples as compared to CTRL samples (AML mean (standard deviation (SD)), 51,829 (27,004) h ng/mL; CTRL mean (SD), 2356 (1250) h ng/mL,
p
= 0.00019). This increase was associated with a prolonged in vitro degradation half-life (
t
1/2IVdeg
AML mean (SD), 15 (11.8) h; CTRL mean (SD), 0.36 (0.37) h,
p
= 0.0033). Multiple linear regression analysis showed that AML diagnosis significantly influenced
t
1/2IVdeg
and AUC
IVlas
relationship.
Conclusion
Cytarabine stability is higher in AML than in CTRL samples. The absence of correlation between
t
1/2IVdeg
and AUC
IVlast
in AML samples suggests that in vitro cytarabine degradation in AML is complex. These results open perspectives including the evaluation of the clinical relevance and the involved molecular mechanisms. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0344-5704 1432-0843 |
DOI: | 10.1007/s00280-020-04150-9 |