Effects of Simvastatin Combined with Rivaroxaban on Pharmacokinetics of Rivaroxaban in Rats
- VernacularTitle:辛伐他汀和利伐沙班联合给药对大鼠体内利伐沙班药动学的影响
- Author:
Feigao LI
1
;
Xueqin ZHANG
1
;
Haoyu WANG
1
;
Guosheng LIU
1
;
Shumei WANG
1
;
Deqiang LI
1
Author Information
1. Dept. of Pharmacy，the Second Hospital of Hebei Medical University，Shijiazhuang 050000，China
- Publication Type:Journal Article
- Keywords:
Rivaroxaban;
Simvastatin;
Pharmacokinetics;
LC-MS/MS;
Rats
- From:
China Pharmacy
2019;30(7):874-877
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To study the effects of simvastatin combined with rivaroxaban on pharmacokinetics of rivaroxaban in rats. METHODS： Thirty rats were randomly divided into rivaroxaban group （intragastric administration of normal saline+rivaroxaban 2.6 mg/kg）， simvastatin+rivaroxaban group （intragastric administration of simvastatin 5.3 mg/kg+rivaroxaban 2.6 mg/kg）， with 15 rats in each group. The rats were given normal saline/simvastatin intragastrically for 5 d， once a day， and then given intragastric administration of rivaroxaban+normal saline/simvastain once. The blood samples were collected from orbital cavity of rats before medication and 0.25， 0.5， 0.75， 1， 1.5， 2， 4， 8， 12， 24 h after medication. The plasma concentration of rivaroxaban was determined by LC-MS/MS. Plasma concentration-time curves were drawn， and the pharmacokinetic parameters were fitted by DAS 2.1.1 software. RESULTS： The pharmacokinetic parameters of rivaroxaban group and simvastatin+rivaroxaban group in rats included that AUC0-24 h were （2 599.86±791.82） and （2 777.74±989.25） ng·h/mL； AUC0-∞ were （3 053.28± 1 116.06） ng·h/mL and （3 396.78±1 409.80） ng·h/mL； t1/2 were （8.06±3.52） h and （9.25±4.18） h； tmax were（0.65±0.28） h and （0.60±0.13） h； CLZ were （0.95±0.32） L/（h·kg） and （0.88±0.34） L/（h·kg）； Vd were（10.37±4.43） L/kg and （11.07±4.48） L/kg； cmax were （424.93±145.30） ng/mL and （507.15±132.40） ng/mL. Compared with rivaroxaban group， AUC0-24 h， AUC0-∞， t1/2， Vd and cmax of simvastatin+rivaroxaban group increased by 6.40％， 10.11％， 12.86％， 6.32％， 16.21％； tmax and CLZ decreased by 8.33％ and 7.95％. There was no significant difference （P＞0.05）. CONCLUSIONS： There is no significant change in pharmacokinetic parameters of rivaroxaban in rats after combination of simvastatin （5.3 mg/kg） and rivaroxaban （2.6 mg/kg）.
