Uridine triacetate

Uridine triacetate is a synthetic uridine pro-drug that is converted to uridine in vivo. When used for the treatment or prevention of toxicity associated with fluorouracil and other antimetabolites, uridine triacetate is utilized for its ability to compete with 5-fluorouracil (5-FU) metabolites for incorporation into the genetic material of non-cancerous cells. It reduces toxicity and cell-death associated with two cytotoxic intermediates: 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). By pre-administering with uridine (as the prodrug uridine triacetate), higher doses of 5-FU can be given allowing for improved efficacy and a reduction in toxic side effects such as neutropenia, mucositis, diarrhea, and hand–foot syndrome.

Uridine triacetate is also used for replacement therapy in the treatment of hereditary orotic aciduria, also known as uridine monophosphate synthase (UMPS) deficiency. As a result of UMPS deficiency, patients experience a systemic deficiency of pyrimidine nucleotides, accounting for most symptoms of the disease. Additionally, orotic acid from the de novo pyrimidine pathway that cannot be converted to UMP is excreted in the urine, accounting for the common name of the disorder, orotic aciduria. Furthermore, orotic acid crystals in the urine can cause episodes of obstructive uropathy. When administered as the prodrug uridine triacetate, uridine can be used by essentially all cells to make uridine nucleotides, which compensates for the genetic deficiency in synthesis in patients with hereditary orotic aciduria.