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Nucleosides Nucleotides Nucleic Acids. 2014;33(4-6):403-12. doi: 10.1080/15257770.2014.894196.

Selection of the best blood compartment to measure cytidine deaminase activity to stratify for optimal gemcitabine or cytarabine treatment.

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1
a Department of Medical Oncology , VU University Medical Center , Amsterdam , The Netherlands.

Abstract

Cytidine deaminase (CDA) plays a crucial role in the degradation of cytidine analogs, such as gemcitabine and cytarabine. Several studies showed that a low CDA activity is associated with more toxicity but a higher efficacy, while a high activity will lead to a lower efficacy but less toxicity. A stratified dosing strategy based on the relative CDA activity would increase efficiency. In order to predict these events, a reliable measurement of CDA with a validated method is crucial. We aimed to determine which phenotype assay would be most suitable; a spectrophotometric assay using cytidine as a substrate, or an HPLC assay using gemcitabine as a substrate. In serum and whole blood of 26 volunteers, both assays showed an excellent correlation (R>0.999), but not in plasma nor in red blood cells. Moreover, there was no difference between males and females. In conclusion, the spectrophotometric assay seems the most simple and cost-effective test. It should be performed in serum, while it should be normalized on protein content as measured by the Bicinchoninic Acid.

KEYWORDS:

Cytidine deaminase; cytarabine; gemcitabine; protein assays

PMID:
24940698
DOI:
10.1080/15257770.2014.894196
[Indexed for MEDLINE]

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