Ngemcitabine metabolism mechanisms of action and self-potentiation pdf

This indirect inhibition of dctd by dfdcdp is due to a reduction in the intracellular dntp pool. Doserelated pharmacologic effects of highdose arac and. Despite such broad use, intrinsic and acquired chemoresistance is common. Used in combination with paclitaxel as firstline therapy for metastatic breast cancer in patients who did not respond to previous anthracyclinecontaining chemotherapy or in whom such chemotherapy was contraindicated. Gemcitabine hydrochloride monograph for professionals. Incorporation of the triphosphate and subsequent inhibition of dna replication and repair appears to be the major mode of.

Gemcitabine is an intravenously administered nucleoside analog chemotherapeutic agent. One of these enzymes, dctd, is inhibited directly by dfdctp and indirectly by dfdcdp heinemann et al. Doserelated pharmacologic effects of highdose arac and its selfpotentiation. Metabolism, mechanisms of action, and selfpotentiation, abstract gemcitabine dfdc is a new anticancer nucleoside that is an analog of deoxycytidine. Gemcitabine is a nucleoside analog that acts by multiple mechanisms. The ability to deliver this agent as an oral drug would allow greater flexibility of administration and patient convenience. Gemcitabine is the firstline treatment for pancreatic adenocarcinoma, but is increasingly used to treat breast, bladder, and nonsmall cell lung cancers. An additional mechanism of action of gemcitabine is selfpotentiation by inhibition of enzymes related to deoxynucleotide metabolism. This interaction is termed selfpotentiation and is evidenced in very few other anticancer drugs. It is a prodrug and, once transported into the cell, must be phosphorylated by deoxycytidine kinase to an active form. Gemcitabine dfdc is a new anticancer nucleoside that is an analog of deoxycytidine. The evidence of its potent antitumor activity in a wide spectrum of in vitro and in vivo tumor models has been successfully confirmed in the clinical setting. Preclinical absorption, distribution, metabolism, and.