Ngemcitabine metabolism mechanisms of action and self-potentiation pdf

This interaction is termed selfpotentiation and is evidenced in very few other anticancer drugs. Gemcitabine is an intravenously administered nucleoside analog chemotherapeutic agent. Gemcitabine is a commonly used antineoplastic agent that is a nucleoside analog and pyrimidine antimetabolite that inhibits rna synthesis. It is a prodrug and, once transported into the cell, must be phosphorylated by deoxycytidine kinase to an active form.

The ability to deliver this agent as an oral drug would allow greater flexibility of administration and patient convenience. Capizzi rl, yang jl, rathmell jp, white jc, cheng e, cheng yc, kute t. Doserelated pharmacologic effects of highdose arac and its selfpotentiation. Despite such broad use, intrinsic and acquired chemoresistance is common. In general, the underlying mechanisms of chemoresistance are poorly understood. Preclinical absorption, distribution, metabolism, and.

Despite structural and pharmacological similarities to arac, gemcitabine displays distinctive features of cellular pharmacology, metabolism and mechanism of action. This indirect inhibition of dctd by dfdcdp is due to a reduction in the intracellular dntp pool. Metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer gemcitabine is the firstline treatment for pancreatic. Doserelated pharmacologic effects of highdose arac and. Gemcitabine hydrochloride monograph for professionals. One of these enzymes, dctd, is inhibited directly by dfdctp and indirectly by dfdcdp heinemann et al. Metabolism, mechanisms of action, and selfpotentiation, abstract gemcitabine dfdc is a new anticancer nucleoside that is an analog of deoxycytidine. Gemcitabine is the firstline treatment for pancreatic adenocarcinoma, but is increasingly used to treat breast, bladder, and nonsmall cell lung cancers. 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. Incorporation of the triphosphate and subsequent inhibition of dna replication and repair appears to be the major mode of.