目的 探究索拉非尼、多纳非尼对艾托格列净在大鼠体内药代动力学的影响，为临床联合用药提供参考。 方法 24只雄性SD大鼠随机分为4组，每组6只。A、B组大鼠分别连续7天灌胃索拉非尼对照溶剂和索拉非尼（100 mg/kg），第7天均灌胃艾托格列净（1.5 mg/kg）；C、D组大鼠分别连续7天灌胃多纳非尼对照溶剂和多纳非尼（40 mg/kg），第7天均灌胃艾托格列净（1.5 mg/kg）。于不同时间点从大鼠眼内眦静脉丛取血，采用超高效液相色谱-串联质谱法测定艾托格列净质量浓度并绘制药-时曲线，应用DAS 2.1.1软件非房室模型计算药代动力学参数。符合正态分布的计量资料两组间比较采用成组t检验，非正态分布的计量资料两组间比较采用Mann-Whitney U秩和检验。 结果 与A组比较，B组艾托格列净药-时曲线下面积（AUC_0-t ）和AUC_0-∞均明显增加（P值均<0.05），半衰期（t_1/2）、平均滞留时间（MRT_0-t ）、MRT_0-∞均显著延长（P值均<0.05），清除率（CL_Z/F）显著降低（P<0.05）；与C组比较，D组艾托格列净的AUC_0-t 、AUC_0-∞均显著增加（P值均<0.01），达峰时间（T_max）、t_1/2、MRT_0-t 、MRT_0-∞均显著延长（P值均<0.01），表观分布容积（V_Z/F）和CL_Z/F均显著降低（P值均<0.05）。 结论 索拉非尼和多纳非尼均能影响艾托格列净在大鼠体内的药代动力学过程，明显增加艾托格列净的体内暴露量，临床联合用药时应密切监测疗效及药物不良反应，必要时给予剂量调整，避免潜在的药物相互作用风险。

Objective To investigate the effect of sorafenib and donafenib on the pharmacokinetics of ertugliflozin in rats， and to provide a theoretical basis for drug combination in clinical practice. Methods A total of 24 male Sprague-Dawley rats were randomly divided into groups A， B， C， and D， with 6 rats in each group. The rats in groups A and B were given sorafenib control solvent and sorafenib （100 mg/kg）， respectively， by gavage for 7 consecutive days， followed by ertugliflozin （1.5 mg/kg） by gavage on day 7. Blood samples were collected from the angular vein plexus at different time points， and ultra-performance liquid chromatography-tandem mass spectrometry was used to determine the mass concentration of ertugliflozin and plot the plasma concentration-time curves， while the non-compartment model in DAS 2.1.1 software was used to calculate related pharmacokinetic parameters. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. Results Compared with group A， group B had significant increases in the AUC_0-t and AUC_0-∞ of the plasma concentration-time curve of ertugliflozin （both P<0.05）， significant prolongation of t_1/2， MRT_0-t， and MRT_0-∞ （all P<0.05）， and a significant reduction in CL_Z/F （P<0.05）. Compared with group C， group D had significant increases in the AUC_0-t and AUC_0-∞ of ertugliflozin （both P<0.05）， significant prolongation of T_max， t_1/2， MRT_0-t， and MRT_0-∞ （all P<0.01）， and significant reductions in V_Z/F and CL_Z/F （both P<0.05）. Conclusion Both sorafenib and donafenib can affect the pharmacokinetics of ertugliflozin in rats and significantly increase the plasma exposure of ertugliflozin. The efficacy and adverse drug reactions of ertugliflozin should be closely monitored during combined use in clinical practice and the dose should be adjusted when necessary to avoid the potential risk of drug interaction.