Bioequivalence and safety of sofosbuvir tablets in the healthy Chinese subjects

Objective To investigate the pharmacokinetic characteristics of sofosbuvir tablets,and to evaluate the bioequivalence and safety of two preparations. Methods Healthy volunteers were recruited through the platform of clinical trial recruitment in The Affiliated Hospital of Changchun University of Chinese Medicine. Screening physical examination was performed for fasting group on September 18,2018 and for postprandial group on September 28,2018,and the volunteers were enrolled after their physical examination results met the inclusion criteria. The fasting group and the postprandial group,with 40 volunteers in each group,were given oral administration of the test preparation sofosbuvir tablets or the reference preparation sofosbuvir tablets( SOVALDI,400 mg). This was a randomized,open-label,two-sequence,four-cycle,single-dose,and completely repeated cross-over bioequivalence test in the fasting or postprandial state in the healthy population; in the fasting group,20 volunteers each received oral administration of the test preparation and the reference preparation,and in the postprandial group,20 volunteers each received oral administration of the test preparation and the reference preparation. Liquid chromatography-tandem mass spectrometry was used to measure the content of sofosbuvir and its major metabolite GS-331007 in human EDTA-K2 plasma; the plasma concentration of sofosbuvir was measured at 15 time points from 0 hour to 8 hours after administration,and that of GS-331007 was measured at 16 time points from 0 hour to 72 hours after administration. WinNonlin software was used to calculate pharmacokinetic parameters and evaluate bioequivalence. Results After the administration of the test preparation and the reference preparation in the fasting state,when the pharmacokinetic parameters of sofosbuvir was used to evaluate the bioequivalence of the test preparation and the reference preparation,the ratios of the geometric means of Cmax,AUC0-t,and AUC0-infwere 90. 55%,97. 26%,and 94. 62%,respectively; when the pharmacokinetic parameters of GS-331007 was used to evaluate the bioequivalence of the test preparation and the reference preparation,the ratios of the geometric means of Cmax,AUC0-t,and AUC0-infwere 98. 91%,98. 98%,and 99. 46%,respec-tively. All of the above values were within the range of 80. 00%-125. 00%. An analysis of variance was performed after the pharmacokinetic parameters of sofosbuvir Cmax,AUC0-t,and AUC0-infwere transformed by natural logarithm,and the results showed that sequence,cycle,and preparation had no marked influence on Cmax,AUC0-t,and AUC0-inf( all P > 0. 05). Conclusion The test preparation of sofosbuvir tablets is bioequivalent to the reference preparation in the fasting and postprandial states.