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29.09.2020 | Short Communication

Slower degradation rate of cytarabine in blood samples from acute myeloid leukemia by comparison with control samples

verfasst von: Chadi Abbara, Guillaume Drevin, Séverine Férec, Sarah Ghamrawi, Simon Souchet, Jean-Baptiste Robin, Aline Schmidt, Mathilde Hunault-Berger, Philippe Guardiola, Marie Briet

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2020

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Abstract

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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Titel: Slower degradation rate of cytarabine in blood samples from acute myeloid leukemia by comparison with control samples
verfasst von: Chadi Abbara
Guillaume Drevin
Séverine Férec
Sarah Ghamrawi
Simon Souchet
Jean-Baptiste Robin
Aline Schmidt
Mathilde Hunault-Berger
Philippe Guardiola
Marie Briet
Publikationsdatum: 29.09.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2020
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04150-9

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Slower degradation rate of cytarabine in blood samples from acute myeloid leukemia by comparison with control samples

Abstract

Purpose

Methods

Results

Conclusion

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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