Gemcitabine is a chemotherapeutic nucleoside that halts DNA synthesis after it is incorporated into an elongating DNA strand. The metabolism of gemcitabine may be affected by polymorphisms in cytidine deaminase.
Chemical structure of gemcitabine: 2',2'-difluorodeoxycytidine
Cytidine deaminase normally metabolizes gemcitabine to an inactive metabolite 2',2'-difluorodeoxyuridine.
A mutation 208G>A in cytidine deaminase results in haplotype *3.
This haplotype is associated with:
(1) a decrease in cytidine deaminase activity, with decrease greater if homozygous
(2) reduced clearance of gemcitabine and elevated plasma levels
(3) increased incidence of significant neutropenia if the patient is also receiving fluorouracil or a platinum-containing drug such as cisplatin
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