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
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篇名: 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
TITLE:
摘要: 目的:研究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。方法:将30只大鼠随机分为利伐沙班组(灌胃生理盐水+利伐沙班2.6 mg/kg)和辛伐他汀+利伐沙班组(灌胃辛伐他汀5.3 mg/kg+利伐沙班2.6 mg/kg),每组15只。各组大鼠先连续灌胃生理盐水/辛伐他汀5 d,每天给药1次,第6天再灌胃利伐沙班+生理盐水/辛伐他汀1次,分别于给药前和末次给药后0.25、0.5、0.75、1、1.5、2、4、8、12、24 h自眼内眦取血0.5 mL,采用液相色谱-串联质谱(LC-MS/MS)法测定大鼠血浆中利伐沙班的质量浓度,绘制药-时曲线,并用DAS 2.1.1软件拟合药动学参数。结果:利伐沙班组和辛伐他汀+利伐沙班组大鼠血浆中利伐沙班的AUC0-24 h分别为 (2 599.86±791.82)、(2 777.74±989.25) ng·h/mL,AUC0-∞分别为(3 053.28±1 116.06)、(3 396.78±1 409.80) ng·h/mL,t1/2分别为(8.06±3.52)、(9.25±4.18) h,tmax分别为(0.65±0.28) h、(0.60±0.13) h,CLZ分别为(0.95±0.32)、(0.88±0.34)L/(h·kg),Vd分别为(10.37±4.43)、(11.07±4.48) L/kg,cmax分别为(424.93±145.30)、(507.15±132.40) ng/mL;与利伐沙班组比较,辛伐他汀+利伐沙班组AUC0-24 h、AUC0-∞、t1/2、、Vd、cmax分别增加了6.40%、10.11%、12.86%、6.32%、16.21%,tmax、CLZ分别降低了8.33%、7.95%,但差异无统计学意义(P>0.05)。结论:辛伐他汀(5.3 mg/kg)与利伐沙班(2.6 mg/kg)联用后,利伐沙班在大鼠体内的药动学参数无显著性变化。
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).
期刊: 2019年第30卷第7期
作者: 李飞高,张学琴,王好雨,刘国盛,王淑梅,李德强
AUTHORS: LI Feigao,ZHANG Xueqin,WANG Haoyu,LIU Guosheng,WANG Shumei,LI Deqiang
关键字: 利伐沙班;辛伐他汀;药动学;高效液相色谱-串联质谱法;大鼠
KEYWORDS: Rivaroxaban; Simvastatin; Pharmacokinetics; LC-MS/MS; Rats
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