非布索坦会耐药吗？

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, the usual treatment for gout is to promote uric acid excretion and inhibit uric acid production, and take 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. It is the latest XOR inhibitor developed in the world. It acts on this oxidase highly selectively, reducing the synthesis of uric acid in the body and lowering the concentration of uric acid, thereby effectively treating ventilation diseases. 

For 30 years, allopurinol has been the only clinical drug used to inhibit the production of uric acid. It has been widely used clinically as a gold treatment drug for gout and has achieved good results in the treatment of gout. Compared with allopurine, febuxostat has obvious advantages: allopurinol only inhibits the reduced form of XOR, while febuxostat has a significant inhibitory effect on both oxidized and reduced forms of XOR, so its uric acid-lowering effect is more powerful and lasting; because 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. Febuxostat is a non-purine XOR inhibitor and therefore has a better safety profile. 

A multicenter, double-blind, randomized phase II clinical study evaluated the safety and efficacy of febuxostat in gout. A total of 136 male and 17 female gout patients were randomly assigned to receive placebo or this product (40, 80 or 120 mg/d). After 4 weeks, tests found that the serum uric acid concentration of patients in each dose group of this product was significantly lower than before treatment, with an average reduction of 37% in each group from low to high. %, 44% and 59%, while patients in the placebo group only decreased by 2%; the vast majority of patients persisted in completing the trial. The incidence rates of adverse reactions in this product and the placebo group were similar, and most of these adverse reactions were mild and self-limiting, with common ones including diarrhea, pain, back pain, headache and joint pain. A phase III clinical trial compared the efficacy of this product (80 and 120 mg/d) with that of allopurinol (300 mg/d). A 1-year study of 760 patients showed that compared with the allopurinol group, more patients in the this product group achieved the main trial efficacy index - the sUA concentration was measured below 60mg/L in the last 3 months (all subjects were gout patients, and the sUA concentration before the test were all above 80mg/L); after 52 weeks of treatment, this product failed to significantly reduce the area of tophi (tophi is a characteristic of gout) Some aggregates of urate crystals), but in the high-dose group early in the trial, this effect was more obvious; in each treatment group, patients with sUA concentration (<60mg/L) were less likely to have gout attacks, and their tophi area was more significantly reduced; adverse reactions and their incidence rates were similar in each treatment group, including abnormal liver function, diarrhea, headache, joint-related signs and symptoms, and musculoskeletal/connective tissue symptoms.

Although febuxostat has remarkable efficacy and mild side effects, there is still a painful fact: any drug will lead to the inevitable end of drug resistance, and this is no exception.