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Fluorouracil is inactive as such in mammalian cells but is converted into the active 5-fluorodeoxyuridine monophosphate (FdUMP) by a variety of different metabolic pathways. The drug works by inhibiting the enzyme thymidylate kinase which results in reduced formation of thymidine and thus of DNA. The active metabolite FdUMP appears to form a stable complex with the folate cofactor N-5, 10-methylene tetrahydrofolate which inactivates thymidylate kinase. Fluorouracil as FdUMP is also incorporated into RNA which results in fluorination of RNA. The effect of fluorouracil on living cells is limited mainly to those in the proliferative phase but while cells in the G2 and S phase are most affected there may be effects at any stage of the cell cycle.
5-fluorouracil is rapidly metabolized in the liver to produce biologically inactive metabolites which are eventually converted to carbon dioxide, eliminated by the lungs. 80% of 5-fluorouracil can be accounted for by conversion to respiratory carbon dioxide within 12 hr of administration. 15% of the drug is excreted through urine.
Fluorouracil is indicated alone or in combination for-
l Carcinoma of the colon or rectum
l Carcinoma of the stomach and exocrine pancreas
l Carcinoma of the liver
l Carcinoma of the breast
l Carcinoma of the bladder
l Carcinoma of the lung
l Epithelial ovarian carcinoma
l Cervical carcinoma
Drucil® Injection 250 mg: Each vial contains 5 ml of solution containing Fluorouracil USP 250 mg as 50 mg/ml.
Drucil® Injection 500 mg: Each vial contains 10 ml of solution containing Fluorouracil USP 500 mg as 50 mg/ml.