title: Selection of the best blood compartment to measure cytidine deaminase activity to stratify for optimal gemcitabine or cytarabine treatment.
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.
authors.affiliation: a Department of Medical Oncology , VU University Medical Center , Amsterdam , The Netherlands.
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Honeywell
authors.forename: Marie
authors.initials: M
authors.lastname: Maulandi
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.forename: Nienke
authors.initials: N
authors.lastname: Losekoot
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Etienne-Grimaldi
authors.forename: Gerard
authors.initials: G
authors.lastname: Milano
authors.forename: Cindy
authors.initials: C
authors.lastname: Serdjebi
authors.forename: Joseph
authors.initials: J
authors.lastname: Ciccolini
mesh_terms: D000328:Adult; D003362:Cost-Benefit Analysis; D003561:Cytarabine / Q000494:pharmacology*; D003564:Cytidine Deaminase / Q000097:blood* / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D057075:Enzyme Assays / Q000191:economics / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D003561:Cytarabine; D003841:Deoxycytidine; D003564:Cytidine Deaminase; D000093542:Gemcitabine
keywords: Cytidine deaminase; cytarabine; gemcitabine; protein assays