高效液相色谱-串联质谱测定人血浆中依普利酮的浓度及其药动学

Determination of eplerenone in human plasma by HPLC-MS/MS and its application to a pharmacokinetic study

目的研究依普利酮片单次及多次给药后的人体药动学。方法 30名健康志愿者分为三组,分别服用依普利酮片50、100、200 mg,其中100 mg组为多次给药组,连续给药7 d;采集24 h内动态血标本,高效液相色谱-串联质谱法测定血浆中依普利酮的浓度,并采用DAS 3.2.4软件对试验数据进行处理,计算药动学参数。结果单次口服50、100和200 mg依普利酮片的主要药动学参数ρ_(max)分别为(723.20±203.59)、(1 212.47±249.52)、(2 053.32±394.06)μg·L^(-1),t_(max)分别为(1.8±0.7)、(2.1±0.9)、(1.9±0.4)h,t_(1/2)分别为(2.6±0.4)、(3.0±0.7)、(3.4±1.3)h,AUC_(0-24h)分别为(3 621.29±1 1 17.37)、(7 492.68±2 031.58)、(13 796.25±4 594.37)μg·h·L^(-1),AUC_(0-∞)分别为(3 710.53±1 144.47)、(7 592.98±2 082.12)、(14 074.54±4 870.39)μg·h·L^(-1)。多次给药100 mg后的药动学参数ρ_(max)为(1 231.83±209.99)μg·L^(-1),t_(max)为(1.7±0.9)h,t_(1/2)为(3.0±0.8)h,AUC_(0-24h)为(7 043.78±1 818.54)μg·h·L^(-1),AUC_(0-∞)为(7 131.65±1 840.84)μg·h·L^(-1)。结论在50~200 mg给药剂量范围内,依普利酮片在体内呈线性动力学特征。

AIM To study the pharmacokinetics of the eplerenone tablets in Chinese healthy volunteers after single- dose and multiple- dose administrations. METHODS Thirty Chinese healthy volunteers were randomly divided to three groups and given eplerenon 50, 100 and 200 mg once daily respectively. The multiple-dose group was administrated with eplerenon 100 mg once daily for 7 days. Intensive blood sampling was performed from thirty volunteers within 24 h after the single dosing and the last dose of the multiple dosing. HPLC- MS/MS method was developed and validated for the determination of eplerenone in plasma. The pharmacokinetic parameters were calculated by DAS 3.2.4 software. RESULTS After a single- dose of the different dose levels （50, 100 and 200 mg） , the main pharmacokinetics parameters of eplerenone were as follows, pmax. were （723.20 ± 203.59）, （1 212.47 ±249.52） and （2 053.32 ± 394.06） μg·L^-1, tmax were （1.8 ± 0.7）, （2.1 ± 0.9） and （1.9± 0.4） h; t1/2 were （2.6 ± 0.4）, （3.0±0.7） and （3.4 ± 1.3） h, AUC0-24h were （3 621.29 ± 1 117.37）, （7 492.68± 2 031.58） and （13 796.25 ± 4 594.37） μg·h·L^-1, AUC0-∞ were （3 710.53 ± 1 144.47）, （7 592.98 ± 2 082.12） and （14 074.54 ± 4 870.39） μg·h·L^-1, respectively. The main pharmacokineties parameters after 100 mg qd for seven days were as follows, pmax was （1 231.83 ± 209.99） μg·h·L^-1, tmax was （1.7 ± 0.9） h, t1/2 was （3.0 ± 0.8） h, AUC0-24h was （7 043.78 ± 1 818.54） μg·h·L^-1, AUC0-∞ was （7 131.65 ± 840.84） μg·h·L^-1. CONCLUSION The pharmacokinetics parameters of eplerenone are linear in the dose range from 50 - 200 mg.