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舒肝解郁胶囊对伏立康唑、利伐沙班和阿哌沙班在大鼠体内药代动力学的影响
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| 篇名： | 舒肝解郁胶囊对伏立康唑、利伐沙班和阿哌沙班在大鼠体内药代动力学的影响 |
| TITLE： | Effects of Shugan jieyu capsules on the pharmacokinetics of voriconazole，rivaroxaban and apixaban in rats |
| 摘要： | 目的 探究舒肝解郁胶囊多次给药对伏立康唑、利伐沙班、阿哌沙班在大鼠体内药代动力学的影响。方法将雄性SD大鼠分为伏立康唑组（30mg/kg）、利伐沙班组（2mg/kg）、阿哌沙班组（0.5mg/kg）、舒肝解郁胶囊+伏立康唑组（145mg/kg+30mg/kg）、舒肝解郁胶囊+利伐沙班组（145mg/kg+2mg/kg）和舒肝解郁胶囊+阿哌沙班组（145mg/kg+0.5mg/kg），每组6只。各组大鼠连续灌胃溶剂（0.5%羧甲基纤维素钠溶液）或舒肝解郁胶囊8d后，再于第8天时分别灌胃伏立康唑、利伐沙班、阿哌沙班药液。于不同时间点（伏立康唑、利伐沙班单用及相应联用组的采血时间为给药前和给药后0.17、0.34、0.5、0.75、1、1.5、2、3、4、5、6、8、10、12h，阿哌沙班单用及相应联用组的采血时间为给药前和给药后0.08、0.17、0.25、0.34、0.5、0.75、1、3、5、7、10、12h）采集血样，采用超高效液相色谱-串联质谱法检测大鼠血浆中伏立康唑、利伐沙班、阿哌沙班的质量浓度，通过非房室模型计算上述药物的主要药代动力学参数并进行组间比较。结果与单用组相比，多次给予舒肝解郁胶囊后，伏立康唑的AUC0－t、AUC0－∞、cmax均显著降低，CLz/F显著增加，tmax显著延长（P＜0.05）；利伐沙班、阿哌沙班的tmax均显著延长（P＜0.05）；而其余药代动力学参数组间比较的差异均无统计学意义（P＞0.05）。结论联用舒肝解郁胶囊可使口服伏立康唑的药物暴露减少、清除增加、达峰延迟；该药虽不影响利伐沙班和阿哌沙班的暴露水平，但会导致两药达峰延迟。 |
| ABSTRACT： | OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole， rivaroxaban and apixaban in rats. METHODS Male SD rats were randomly divided into voriconazole group （30 mg/kg）， rivaroxaban group （2 mg/kg）， apixaban group （0.5 mg/kg）， Shugan jieyu capsules+voriconazole group （145 mg/kg+30 mg/kg）， Shugan jieyu capsules+rivaroxaban group （145 mg/kg+2 mg/kg）， Shugan jieyu capsules+apixaban group （145 mg/kg+0.5 mg/kg）， with 6 rats in each group. After the rats in each group were consecutively administered solvent （0.5% sodium carboxymethyl cellulose solution） or Shugan jieyu capsules by intragastric gavage for 8 days， they were respectively given voriconazole， rivaroxaban and apixaban solution by intragastric gavage on the 8th day. Blood samples were then collected at different time points （in voriconazole group， rivaroxaban group and corresponding drug combination groups， blood was collected before administration and at 0.17， 0.34， 0.5， 0.75， 1， 1.5， 2， 3， 4， 5， 6， 8， 10 and 12 hours post-administration； in apixaban group and corresponding drug combination group， blood was collected before administration and at 0.08， 0.17， 0.25， 0.34， 0.5， 0.75， 1， 3， 5， 7， 10 and 12 hours post-administration）. Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole， rivaroxaban and apixaban in rat plasma. The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model， and the comparisons were made between groups. RESULTS Compared with single drug group， after multiple administrations of Shugan jieyu capsules， AUC0－t， AUC0－∞ and cmax of voriconazole were significantly decreased， while CLz/F was significantly increased， and tmax was also significantly prolonged （P＜0.05）. For rivaroxaban and apixaban， their tmax values were both significantly prolonged （P＜0.05）. However， there were no statistically significant differences in the other pharmacokinetic parameters between the two groups （P＞0.05）. CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure， increase the clearance， and delay the peak concentration of oral voriconazole. However， it does not affect the exposure levels of rivaroxaban and apixaban， but it does delay the time to reach peak concentration for both drugs. |
| 期刊： | 2025年第36卷第12期 |
| 作者： | 李颖；单春辉；宋怡瑧；马银玲；王智；郭彩会；董占军 |
| AUTHORS： | LI Ying，SHAN Chunhui，SONG Yizhen，MA Yinling，WANG Zhi，GUO Caihui，DONG Zhanjun |
| 关键字： | 舒肝解郁胶囊；伏立康唑；利伐沙班；阿哌沙班；药物相互作用；药代动力学 |
| KEYWORDS： | Shugan jieyu capsules； voriconazole； rivaroxaban； apixaban； drug-drug interaction； pharmacokinetics |
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