中国药房2025，Vol.36Issue(12)：1470-1475,6.DOI:10.6039/j.issn.1001-0408.2025.12.09
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
Effects of Shugan jieyu capsules on the pharmacokinetics of voriconazole,rivaroxaban and apixaban in rats
摘要
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.关键词
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Key words
Shugan jieyu capsules/voriconazole/rivaroxaban/apixaban/drug-drug interaction/pharmacokinetics分类
医药卫生引用本文复制引用
李颖,单春辉,宋怡瑧,马银玲,王智,郭彩会,董占军..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[J].中国药房,2025,36(12):1470-1475,6.基金项目
河北省自然科学基金项目(No.H2022307063) （No.H2022307063）
