Despite structural and pharmacological similarities to arac, gemcitabine displays distinctive features of cellular pharmacology, metabolism and mechanism of action. Gemcitabine is a nucleoside analog that acts by multiple mechanisms. Capizzi rl, yang jl, rathmell jp, white jc, cheng e, cheng yc, kute t. Gemcitabine hydrochloride monograph for professionals. Doserelated pharmacologic effects of highdose arac and its selfpotentiation. This indirect inhibition of dctd by dfdcdp is due to a reduction in the intracellular dntp pool. Doserelated pharmacologic effects of highdose arac and. Gemcitabine is a commonly used antineoplastic agent that is a nucleoside analog and pyrimidine antimetabolite that inhibits rna synthesis. An additional mechanism of action of gemcitabine is selfpotentiation by inhibition of enzymes related to deoxynucleotide metabolism. The ability to deliver this agent as an oral drug would allow greater flexibility of administration and patient convenience. This interaction is termed selfpotentiation and is evidenced in very few other anticancer drugs. Gemcitabine is the firstline treatment for pancreatic adenocarcinoma, but is increasingly used to treat breast, bladder, and nonsmall cell lung cancers. Preclinical absorption, distribution, metabolism, and. It is a prodrug and, once transported into the cell, must be phosphorylated by deoxycytidine kinase to an active form.
Incorporation of the triphosphate and subsequent inhibition of dna replication and repair appears to be the major mode of. 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. In general, the underlying mechanisms of chemoresistance are poorly understood. 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. 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.
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