Effects of Simvastatin Combined with Rivaroxaban on Pharmacokinetics of Rivaroxaban in Rats / 中国药房

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）.