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

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

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.

MeSH terms

  • Adult
  • Cost-Benefit Analysis
  • Cytarabine / pharmacology*
  • Cytidine Deaminase / blood*
  • Cytidine Deaminase / metabolism*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Enzyme Assays / economics
  • Enzyme Assays / methods*
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Reproducibility of Results
  • Young Adult

Substances

  • Cytarabine
  • Deoxycytidine
  • Cytidine Deaminase
  • Gemcitabine