Evaluation of the pharmacokinetics and food intake effect of generic sofosbuvir in healthy Chinese subjects .

OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.