Abstract
Protracted intravenous infusions of fluorouracil (5-FU) in the treatment of colorectal cancer have been associated with a reduction in toxicity and enhanced clinical activity compared with bolus 5-FU schedules. However, these protracted infusions require portable infusion pumps and central venous lines, which are associated with complications of venous thrombosis, infection, and line slippage. An effective oral 5-FU formulation could provide a more convenient protracted treatment method with fewer complications. Because of its inconsistent and erratic absorption, the use of oral 5-FU was abandoned decades ago. The inconsistent absorption of oral 5-FU may be attributed to varying levels of dihydropyrimidine dehydrogenase (DPD) in the gastrointestinal tract. Two methods have been used to circumvent 5-FU's metabolism by DPD in the gastrointestinal tract. First, DPD may be inactivated, allowing for reliable, consistent absorption of 5-FU. Second, 5-FU prodrugs can be administered, being absorbed as intact molecules via the gastrointestinal tract and subsequently converted to 5-FU. The oral fluoropyrimidines discussed here are capable of providing prolonged 5-FU exposure with a reduced incidence of toxicity.
MeSH terms
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Animals
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Antimetabolites, Antineoplastic / pharmacology
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Antimetabolites, Antineoplastic / therapeutic use*
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Capecitabine
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Colorectal Neoplasms / drug therapy*
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Deoxycytidine / analogs & derivatives
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Deoxycytidine / pharmacology
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Deoxycytidine / therapeutic use
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Dihydrouracil Dehydrogenase (NADP)
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Drug Combinations
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use*
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Fluorouracil / analogs & derivatives
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Fluorouracil / pharmacology
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Fluorouracil / therapeutic use*
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Folic Acid Antagonists / pharmacology
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Folic Acid Antagonists / therapeutic use*
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Humans
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Leucovorin / pharmacology
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Leucovorin / therapeutic use
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Oxidoreductases / antagonists & inhibitors*
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Oxonic Acid / pharmacology
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Oxonic Acid / therapeutic use
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Prodrugs / pharmacology
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Prodrugs / therapeutic use*
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Pyridines / pharmacology
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Pyridines / therapeutic use
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Tegafur / pharmacology
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Tegafur / therapeutic use
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Uracil / analogs & derivatives
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Uracil / pharmacology
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Uracil / therapeutic use
Substances
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Antimetabolites, Antineoplastic
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Drug Combinations
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Enzyme Inhibitors
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Folic Acid Antagonists
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Prodrugs
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Pyridines
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UFT(R) drug
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Deoxycytidine
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S 1 (combination)
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Tegafur
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eniluracil
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Uracil
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Oxonic Acid
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Capecitabine
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Emitefur
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Oxidoreductases
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Dihydrouracil Dehydrogenase (NADP)
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Leucovorin
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Fluorouracil