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目的研究依普利酮片在中国健康受试者体内单次及多次给药的药动学特征。方法 12名受试者(男、女各半),按3×3拉丁方设计分别交叉口服依普利酮片25,50,100 mg,进行单次给药药动学研究;10名受试者(男、女各半)连续给药6 d,每天1次,每次50 mg,进行多次给药药动学研究。血药浓度用LC-MS/MS快速测定。结果 12名受试者单次给药25,50,100mg依普利酮后,ρmax分别为(450.2±146.2)、(765.2±258.2)、(1 262±428)μg.L-1,tmax分别为(1.71±0.33)、(2.06±1.01)、(2.79±1.48)h,t1/2分别为(2.50±0.39)、(2.69±0.55)、(2.84±0.53)h,AUC0-24 h分别为(2 410±778)、(4 403±1 522)、(8 202±2 398)μg.h.L-1,AUC0-∞分别为(2 429±774)、(4 426±1 523)、(8 246±2 407)μg.h.L-1;10名受试者单次给药50 mg和多次给药50 mg依普利酮达到稳态后,tmax分别为(3.40±1.27)和(2.65±1.00)h,t1/2分别为(3.03±0.66)和(3.22±0.62)h,ρmax和ρSmSax分别为(690.7±207.4)和(743.2±192.3)μg.L-1,ρSmSin为(12.81±9.64)μg.L-1,ρSavS为(219.0±59.6)μg.L-1,AUCSS为(5 256±1 431)μg.h.L-1。结论口服给药剂量范围在25～100 mg时,依普利酮在人体内具有线性药动学特征;依普利酮按每日给药1次,每次口服50 mg,连续给药6 d在人体内不会产生蓄积。
Objective To study the pharmacokinetic characteristics of eplerenone tablets in single and multiple administrations in healthy Chinese subjects. Methods Twelve subjects (half male and half female) were enrolled in this study. Each eplerenone tablet (25, 50, 100 mg) was orally administered in a 3 × 3 Latin square design for single-dose pharmacokinetic studies. Ten subjects Male and female halves) for 6 consecutive days, once daily, each 50 mg, multiple pharmacokinetic studies. Plasma concentration was determined rapidly by LC-MS / MS. Results After administration of 25, 50 and 100 mg eplerenone alone, the mean ρmax of the 12 subjects were (450.2 ± 146.2), (765.2 ± 258.2) and (1262 ± 428) μg.L-1, respectively (2.71 ± 0.33), (2.06 ± 1.01) and (2.79 ± 1.48) h respectively, and the values of t1 / 2 were 2.50 ± 0.39, 2.69 ± 0.55 and 2.84 ± 0.53 h, respectively AUC0-∞ were (2 429 ± 774), (4226 ± 1 523), (846 ± 1 523) and (842 ± 2 398) μg.hL- ± 2 407) μg.hL-1. The tmax was (3.40 ± 1.27) and (2.65 ± 1.00), respectively, in 10 subjects after single administration of 50 mg and repeated administration of 50 mg of eplerenone ) h and t1 / 2 were (3.03 ± 0.66) and (3.22 ± 0.62) h, respectively. The values of ρmax and ρSmSax were (690.7 ± 207.4) and (743.2 ± 192.3) μg.L- μg · L-1, ρSavS was (219.0 ± 59.6) μg.L-1, and AUCSS was (5 256 ± 1 431) μg.hL-1. Conclusion Eplerenone possesses linear pharmacokinetics in the human body when the oral administration dose is in the range of 25 ~ 100 mg. Eplerenone is administered once daily, 50 mg orally for 6 days In the human body will not produce accumulation.