目的 通過¹⁴C同位素標(biāo)記技術(shù)研究[¹⁴C]瑪舒拉沙韋混懸液在男性健康受試者中的放射性藥動學(xué)行為、物質(zhì)平衡和代謝轉(zhuǎn)化途徑。方法 采用單中心、開放、非隨機、單劑量、空腹?fàn)顟B(tài)下的口服給藥試驗。6名健康男性受試者空腹服用40 mg（約100 μCi）[¹⁴C]瑪舒拉沙韋混懸液，采集全血、血液、尿液、糞便，根據(jù)總放射性、瑪舒拉沙韋及其代謝產(chǎn)物的血藥濃度，通過非房室模型估算藥動學(xué)參數(shù)；通過尿樣和糞樣中的濃度，計算藥物累積排泄量，提供物質(zhì)平衡數(shù)據(jù)。結(jié)果 血漿中未檢測到瑪舒拉沙韋，血漿中主要放射性物質(zhì)為代謝產(chǎn)物GP1707D07，其暴露量占總放射性物質(zhì)的95.4%。GP1707D07與總放射性物質(zhì)的藥動學(xué)特征相近。在0～336 h時段，尿和糞中放射性物質(zhì)總回收率為90.1%，其中糞樣中總放射性占84.1%。除原形藥外，在人體內(nèi)共鑒定了8個代謝產(chǎn)物。在人體內(nèi)最主要代謝途徑是經(jīng)O-去烷基化生成代謝產(chǎn)物M2。結(jié)論 在健康受試者中瑪舒拉沙韋原藥在體內(nèi)快速代謝，血漿中主要成分為其活性代謝產(chǎn)物GP1707D07，其代謝產(chǎn)物不傾向分布于血細(xì)胞，且在全血中的消除比血漿中的稍慢，瑪舒拉沙韋及其代謝產(chǎn)物主要經(jīng)糞便排泄。

Objective To study the radiopharmacokinetic behavior, mass balance, and metabolic transformation pathway of [¹⁴C] Suraxavir Marboxil Suspension in healthy male subjects by ¹⁴C isotope labeling technique. Methods A single-center, open, nonrandomized, single-dose, fasting oral administration trial was designed. Six healthy male subjects were po administered with 40 mg (approximately 100 µCi)[¹⁴C] Suraxavir Marboxil Suspension on an empty stomach. The whole blood, blood, urine, and stool were collected. The pharmacokinetic parameters were estimated by non-atrioventricular model according to total radioactivity and the blood concentration data of Suraxavir Marboxil and its metabolites. The cumulative excretion of drugs was calculated by the concentration data in urine and stool samples obtained to provide material balance data. Results Suraxavir marboxil was not detected in the plasma, and the main radioactive substance in the plasma was the metabolite GP1707D07, and its exposure accounted for 95.4% of the total radioactive substance. The pharmacokinetic characteristics of GP1707D07 were similar to those of total radioactive material. During the 0 — 336 h period, the total recovery rate of radioactive substances in urine and feces was 90.1%, with 84.1% of the total radioactivity in fecal samples. In addition to the original drug, a total of 8 metabolites were identified in the human body. The main metabolic pathway in the human body was the generation of metabolite M2 through O-dealkylation. Conclusion In healthy subjects, the suraxavir marboxil original drug is rapidly metabolized in the body, and its main component in plasma is its active metabolite GP1707D07. Its metabolite does not tend to be distributed in blood cells and its elimination in whole blood is slightly slower than those in plasma. Suraxavir marboxil and its metabolites are mainly excreted through feces.

R969.1