关键词: 索拉非尼, 生物等效性, 药代动力学

Abstract: AIM: To compare the pharmacokinetic behavior of a single oral sorafenib tosylate tablets in Chinese healthy subjects under fasting conditions and evaluate the bioequivalence of the test reagent (T) and the reference reagent (R).  METHODS: A single-center, randomized, open-labeled, two-agent, three-period, three-sequence (TRR, RTR, RRT), and partially repeated crossover trial design was adopted. The trial was administered once per cycle (0.2 g) under fasting conditions. 36 healthy subjects were randomly divided into 3 groups, each with 12 cases. RESULTS: Thirty-six healthy subjects (9 females, average age 31 years) were enrolled in the trial. The upper limits of the one-sided 95% confidence interval of the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞ of the test reagent and the reference reagent after natural logarithmic transformation were －0.0908, －0.0577, －0.0541. The one-sided 95% upper limit of the confidence interval was less than 0; the ratios of the geometric mean values of the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞ of sorafenib of the test preparation and the reference preparation were 101.65%, 100.12%, and 99.24%, respectively. In the range of 80.00%-125.00%, the bioequivalence of Cmax, AUC0-t and AUC0-∞ of the test reagent and the reference reagent sorafenib was established under the fasting state. CONCLUSION: The safety and tolerability of a single oral 0.2 g sorafenib tosylate tablet by subjects under fasting conditions were good. The test reagent and the reference reagent are bioequivalent under fasting administration.

Key words: sorafenib, bioequivalence, pharmacokinetics