Effects of Shugan jieyu capsules on the pharmacokinetics of voriconazole，rivaroxaban and apixaban in rats
- VernacularTitle: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
- Author:
Ying LI
1
,
2
;
Chunhui SHAN
3
;
Yizhen SONG
4
;
Yinling MA
1
;
Zhi WANG
1
;
Caihui GUO
1
;
Zhanjun DONG
1
Author Information
1. Dept. of Pharmacy，Hebei General Hospital，Shijiazhuang 050051，China
2. Hebei Key Laboratory of Clinical Pharmacy，Shijiazhuang 050051，China
3. Dept. of Medical Imaging，Hebei General Hospital，Shijiazhuang 050051，China
4. School of Pharmacy，Hebei Medical University，Shijiazhuang 050017，China
- Publication Type:Journal Article
- Keywords:
Shugan jieyu capsules;
voriconazole;
rivaroxaban;
apixaban;
drug-drug interaction;
pharmacokinetics
- From:
China Pharmacy
2025;36(12):1470-1475
- CountryChina
- Language:Chinese
-
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.
