Li Xin, Liu Yujie, Xu Bing, Liu Lihua, Li Yuan, Zhang Ping, Wang Yiya
Int J Clin Pharmacol Ther. 2020 Apr;58(4):230-241. doi: 10.5414/CP203649.
Sofosbuvir is an NS5B nucleotide inhibitor that was approved for hepatitis C treatment. Generic sofosbuvir has been produced to improve the affordability. The present study investigated the pharmacokinetics (PK) and safety of generic sofosbuvir as well as the effect of food intake on its PK parameters in healthy Chinese subjects.
This open-label, randomized, multiple-dose, dose-escalating, and food effect trial enrolled 12 healthy Chinese subjects. The subjects received a single oral dose of 400 mg of generic sofosbuvir in fasted state or after a high-fat meal, or 800 mg in fasted state, in a three-way crossover design, and then all subjects were administered with 400 mg daily for 8 days. The PK parameters for sofosbuvir and its metabolites were determined, and the safety was monitored.
Sofosbuvir was absorbed rapidly into plasma, with a half-life of 0.46 - 0.48 hours. Plasma exposure to sofosbuvir and its metabolite GS-566500 was increased in an approximately proportional manner to the increased dose. Repeated dosing did not result in drug accumulation in the blood. Sofosbuvir was mainly excreted as the metabolite GS-331007 in the urine. Drug administration after a high-fat meal increased the plasma sofosbuvir exposure by 1.29-fold, without substantially altering the absorption rate. No serious adverse events were observed, and all subjects tolerated the doses well.
This generic sofosbuvir was well absorbed, the plasma concentration was increased with an increased dose, and it was safe in healthy subjects. A high-fat meal appeared to promote the bioavailability of sofosbuvir and the metabolite GS-566500.
索磷布韦是一种获批用于治疗丙型肝炎的NS5B核苷酸抑制剂。已生产出索磷布韦仿制药以提高其可及性。本研究调查了索磷布韦仿制药在健康中国受试者中的药代动力学（PK）和安全性，以及食物摄入对其PK参数的影响。
本开放标签、随机、多剂量、剂量递增及食物效应试验纳入了12名健康中国受试者。受试者采用三交叉设计，在禁食状态下或高脂餐后接受单次口服400 mg索磷布韦仿制药，或在禁食状态下接受800 mg索磷布韦仿制药，然后所有受试者每日服用400 mg，持续8天。测定索磷布韦及其代谢产物的PK参数，并监测安全性。
索磷布韦迅速吸收入血浆，半衰期为0.46 - 0.48小时。血浆中索磷布韦及其代谢产物GS-566500的暴露量随剂量增加呈近似比例增加。重复给药未导致药物在血液中蓄积。索磷布韦主要以代谢产物GS-331007的形式经尿液排泄。高脂餐后给药使血浆中索磷布韦的暴露量增加了1.29倍，而吸收速率未发生实质性改变。未观察到严重不良事件，所有受试者对剂量耐受性良好。
这种索磷布韦仿制药吸收良好，血浆浓度随剂量增加而升高，在健康受试者中是安全的。高脂餐似乎可促进索磷布韦及其代谢产物GS-566500的生物利用度。
