The introduction of the hypomethylating agents azacitidine and decitabine has been a major advancement in the treatment of patients with higher‐risk myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia who are ineligible for more intensive treatments. This concise drug review summarizes the current state of treatment with azacitidine and decitabine.

Keywords 5-fluorouracil, 5-fluorouridine triphosphate (FUTP), capecitabine, nucleotides, peripheral blood mononuclear cells (PBMCs), pharmacokinetics AIM Three intracellularly formed metabolites are responsible for the antineoplastic effect of capecitabine: 5-fluorouridine 5′-triphosphate (FUTP), 5-fluoro-2′-deoxyuridine 5′-triphosphate (FdUTP), and 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP). The objective of this study was to explore the pharmacokinetics of these intracellular metabolites during capecitabine treatment. METHODSSerial plasma and peripheral blood mononuclear cell (PBMC) samples were collected from 13 patients treated with capecitabine 1000 mg QD (group A) and eight patients receiving capecitabine 850 mg m À2 BID for fourteen days, every three weeks (group B). Samples were collected on day 1 and, for four patients of group B, also on day 14. The capecitabine and 5-fluorouracil (5-FU) plasma concentrations and intracellular metabolite concentrations were determined using LC-MS/MS. Pharmacokinetic parameters were estimated using non-compartmental analysis. RESULTSOnly FUTP could be measured in the PBMC samples. The FdUTP and FdUMP concentrations were below the detection limits (LOD). No significant correlation was found between the plasma 5-FU and intracellular FUTP exposure. The FUTP concentrationtime profiles demonstrated considerable inter-individual variation and accumulation of the metabolite in PBMCs. FUTP levels ranged between

The study provides the first complete picture of all nucleotides that are formed intracellularly during gemcitabine treatment. Low intracellular dFdU nucleotide concentrations were found, which calls into question the relevance of these nucleotides for the cytotoxic effects of gemcitabine.