Gemcitabine metabolism

Plunkett W, Huang P, Xu YZ, Heinemann V, Grunewald R, Gandhi V. Gemcitabine metabolism, mechanisms of action, and self-potentiation. Semin Oncol 1995 22(4 Suppl 11) 3—10. 

Gemcitabine (Fig. 7) is a cytosine derivative that is very similar to ara C. It undergoes metabolic activation to difluorodeoxycytidine triphosphate, which interferes... 

X. Song, P. L. Lorenzi, C. P. Landowski, B. S. Vig, J. M. Hilfinger, and G. L. Amidon. Amino acid ester prodrugs of the anticancer agent gemcitabine synthesis, bioconversion, metabolic bioevasion, and hPEPTl-mediated transport. Mol Pharm 2 157-167 (2005). 

The biologic action of gemcitabine on its own is due almost completely to its effects on DNA metabolism. Early studies of this drug in leukemic cell lines showed that notable decreases in cellular dNTPs occurred with the use of the drug (8). These decreases were most impressive in terms of the levels of 2 -deoxycytidine 5 -triphosphate (dCTP), however, 2 -deoxyadenosine 5 -triphosphate (dATP) and 2 -deoxyguanosine 5 -triphosphate (dGTP) were also affected. It is felt that part of this is due to the inhibitory effects of... 

Gemcitabine is intracellularly activated by nucleoside kinases to diphosphate and triphosphate nucleosides. Gemcitabine diphosphate inhibits DNA synthesis by inhibiting ribonucleotide reductase while gemcitabine triphosphate competes with deoxycytidine triphosphate for incorporation into DNA. Gemcitabine is used for the treatment of non-small cell lung carcinoma and of adenocarcinoma of the pancreas. It has to be administred intravenously and is eliminated by metabolism with an elimination half-life of approximately 50 minutes. Its spectrum of adverse effects is comparable to that of 5-FU. 

Gemcitabine (Gemzar), an antimetabolite, undergoes metabolic activation to difluorodeoxycytidine triphosphate, which interferes with DNA synthesis and repair, ft is the single most active agent for the treatment of metastatic pancreatic cancer, and it is used as a first-line treatment for both pancreatic and small cell lung cancer. It is administered by intravenous infusion. The dose-limiting toxicity is bone marrow suppression. 

Scheme 4.12 Examples of fluorine

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