盐酸沙格雷酯对酒石酸美托洛尔片药动学的影响

Effect of Sarpogrelate Hydrochloride on the Pharmacokinetics of Metoprolol Tartrate Tablets

建立了超高效液相色谱法测定大鼠血浆中的酒石酸美托洛尔,并考察盐酸沙格雷酯对酒石酸美托洛尔在大鼠体内药动学的影响。选用拉莫三嗪为内标,Acquity UPLC[R]BEH C18色谱柱,以甲醇∶0.01 mol/L磷酸二氢钾缓冲液（加磷酸调至p H 3.6）（31∶69）为流动相,检测波长225 nm。40只Wistar大鼠随机分为2组,每组20只,对照组灌胃给予酒石酸美托洛尔27 mg/kg,试验组灌胃给予盐酸沙格雷酯10 mg/kg和酒石酸美托洛尔27 mg/kg。用DAS 2.1.1软件拟合药动学参数,并以SPSS 13.1软件比较2组的药动学参数。结果表明,试验组的AUC0→5 h、AUC0→∞、t1/2、tmax、V、CL和cmax与对照组相比无显著性差异（P〉0.05）。合用盐酸沙格雷酯前后酒石酸美托洛尔在大鼠体内的药动学无显著性变化。

An UPLC method was established for the determination of metoprolol tartrate in rat plasma. The influence of sarpogrelate hydrochloride on the pharmacokinetics of metoprolol tartrate in rats was also investigated. An Acquity UPLC BEH C18 column was used, with lamotrigine as the internal standard and the mobile phase of methanol ： 0.01 mol/Lpotassium dihydrogen phosphate buffer （adjusted to pH 3.6 with phosphoric acid） （31 ： 69）, at the detection wavelength of 225 nm. Forty rats were randomly divided into two groups with 20 rats in each. Each rat in the control group was given metoprolol tartrate （27 mg/kg） by gavage, while the animal in the test group was given metoprolol tartrate （27 mg/kg） and sarpogrelate hydrochloride （10 mg/kg） by gavage. The pharmacokinetic parameters of the two groups were calculated by DAS 2.1.1 pharmacokinetic software and were compared by SPSS 13.1 software. The results showed that there were no significant differences of the AUC0→5 h, AUC0→∞ t1/2, tmax, V, CL and Cmax between the control group and the test group （P〉0.05）. It suggested that the pharmacokinetics of metoprolol tartrate in rats had no significant difference between single administration and co-administration with sarpogrelate hydrochloride.