非布司他的获批适应症

It is a xanthine oxidase (XO) inhibitor approved for the chronic management of patients with hyperuricemic gout. Gout occurs due to excessive production of uric acid in the body and reduced kidney clearance ability. Uric acid accumulates in the body, leading to the deposition of urate crystals in joints and various organs. Therefore, gout is usually treated by promoting uric acid excretion and inhibiting uric acid production, and taking appropriate measures to improve related symptoms. The production of uric acid in the body is related to purine metabolism. In the final step of purine metabolism, hypoxanthine generates xanthine under the action of xanthine oxidoreductase (XOR), and then further generates uric acid. Inhibiting the activity of this enzyme can effectively reduce the production of uric acid. Febuxostat is the latest XOR inhibitor developed in the world. It acts highly selectively on this oxidase to reduce the synthesis of uric acid in the body and lower the concentration of uric acid, thereby effectively treating gout.

Febuxostat is a potent non-purine selective inhibitor of xanthine oxidase (XO). By selectively inhibiting xanthine oxidase, it can achieve the therapeutic effect of reducing serum uric acid. Uric acid is the end product of purine metabolism and is produced in the cascade reaction of hypoxanthine → xanthine → uric acid. Each step of the conversion is catalyzed by xanthine oxidase. Febuxostat has been shown to effectively inhibit both the oxidized and reduced forms of xanthine oxidase. Febuxostat at therapeutic concentrations does not inhibit other enzymes involved in purine or pyrimidine metabolism, namely guanine deaminase, hypoxanthine guanine phosphoribosyltransferase, orotate phosphoribosyltransferase, orotate monophosphate decarboxylase, or purine nucleoside phosphorylase. 

Compared with allopurine, febuxostat has obvious advantages: (1) Allopurinol only inhibits the reduced XOR, while febuxostat has a significant inhibitory effect on both oxidized and reduced XOR, so its effect of reducing uric acid is more powerful and lasting; (2) Since allopurinol is a purine analogue, it inevitably affects the activities of other enzymes involved in purine and pyridine metabolism. Therefore, repeated high-dose administration is required to maintain high drug levels during allopurinol treatment. This also leads to serious or even fatal adverse reactions due to drug accumulation. It is a non-purine XOR inhibitor and therefore has better safety profile.