Thomas Sonia Amin, Tomeh Neveen, Theard Stephanie
Philadelphia School of Osteopathic Medicine School of Pharmacy, North Fulton Hospital, Suwanee, GA, U.S.A.
Anticancer Res. 2015 Dec;35(12):6761-3.
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.
氟尿嘧啶（5-FU；艾得新®）是一种嘧啶类似物抗肿瘤化疗药物，其作用机制是干扰DNA和RNA的合成。它有一种罕见的毒性，称为高氨血症性脑病。这种神经毒性与高剂量使用5-FU（2600mg/m²/周）有关，发生率为5.7%，而目前1200mg/m²在46小时内输注的剂量通常不会出现这种情况。这种神经毒性背后的机制尚不清楚，但可能是由于5-FU代谢副产物氟柠檬酸的积累。这种副产物抑制三羧酸循环，导致依赖三磷酸腺苷的尿素循环受损。通过损害这个循环，氨不能转化为尿素，进而导致氨的积累。大脑中积累的氨被代谢为谷氨酰胺，有人认为这会导致颅内压升高和脑水肿。本病例报告讨论了一名40岁的结肠癌男性如何经历5-FU诱导的高氨血症并接受治疗，以及将剂量降低50%如何导致该症状不再复发。
