title: Fluorouracil-induced Hyperammonemia in a Patient with Colorectal Cancer.
abstract: Fluorouracil (5-FU; Adrucil®) is a pyrimidine analog antineoplastic chemotherapy agent which works by interfering with DNA and RNA synthesis. It has an uncommon toxicity called hyperammonemic encephalopathy. This neurotoxicity is associated with a high-dose administration of 5-FU (2,600 mg/m(2)/week), with an incidence rate of 5.7%, and is not normally seen with the current dose of 1,200 mg/m(2) infused over 46 h. The mechanism behind this neurotoxicity is not known but is possibly due to accumulation of fluorocitrate, a byproduct of 5-FU metabolism. This by-product inhibits the Krebs cycle, which causes impairment of the adenosine triphosphate-dependent urea cycle. By impairing this cycle, ammonia is not converted to urea, which in turn this leads to an accumulation of ammonia. The accumulated ammonia in the brain is metabolized to glutamine, which has been suggested to cause an increase in intracranial pressure and cerebral edema. This case report discusses how a 40-year-old male with colorectal cancer experienced 5FU-induced hyperammonemia and was treated for it and how reducing the dose by 50% led to resolution of this symptom from reoccurring.
authors.affiliation: Philadelphia School of Osteopathic Medicine School of Pharmacy, North Fulton Hospital, Suwanee, GA, U.S.A. soniapa@pcom.edu.
authors.forename: Sonia Amin
authors.initials: SA
authors.lastname: Thomas
authors.affiliation: Philadelphia School of Osteopathic Medicine School of Pharmacy, North Fulton Hospital, Suwanee, GA, U.S.A.
authors.forename: Neveen
authors.initials: N
authors.lastname: Tomeh
authors.affiliation: Philadelphia School of Osteopathic Medicine School of Pharmacy, North Fulton Hospital, Suwanee, GA, U.S.A.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Theard
mesh_terms: D000328:Adult; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000009:adverse effects*; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced*; D008297:Male
chemical_list: D005472:Fluorouracil
keywords: Fluorouracil; colorectal cancer; fluorocitrate; hyperammonemia