Lee Soo-Yun, Kim Jung-Ryul, Jung Jin Ah, Kim Tae-Eun, Lee Soo-Youn, Huh Wooseong, Lee Jae-Won, Jun Hun, Ko Jae-Wook
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Busan, Seoul, Republic of Korea.
Pharmacology. 2015;96(1-2):68-75. doi: 10.1159/000430889. Epub 2015 Jun 18.
To compare the pharmacokinetics, pharmacodynamics, and safety of sarpogrelate between controlled-release (CR) and immediate-release (IR) formulations after multiple-dose administration.
This study was a randomized, open-label, 2-period, 2-treatment, crossover study in healthy subjects. All subjects received CR sarpogrelate 300 mg once daily and IR sarpogrelate 100 mg three times daily by random order each for 3 days with a 7-day washout period. Serial blood sampling was performed over 24 h. Pharmacokinetic parameters were determined by noncompartmental methods. Platelet aggregation to collagen, measured by light transmission aggregometry, was reported as maximal platelet aggregation.
Thirty-two subjects completed the study. CR sarpogrelate increased rapidly, reaching Cmax in 1.25 h (vs. 1.00 h in IR sarpogrelate) and declined with a t1/2 of 3.59 h (vs. 1.12 h in IR sarpogrelate). The 90% CIs for the geometric mean ratio of AUCτ and Cmax,ss between IR and CR formulations were 1.18 to 1.40 and 0.99 to 1.29, respectively. The degree of inhibition of platelet aggregation was similar between two formulations.
CR sarpogrelate showed slightly higher systemic exposure and similar peak concentration compared with IR sarpogrelate. The profiles of pharmacodynamics and safety were comparable between two formulations.
比较多剂量给药后，缓释（CR）和速释（IR）制剂的沙格雷酯的药代动力学、药效学及安全性。
本研究为一项针对健康受试者的随机、开放标签、2期、2治疗组、交叉研究。所有受试者按随机顺序分别接受300mg CR沙格雷酯每日一次和100mg IR沙格雷酯每日三次，各给药3天，洗脱期为7天。在24小时内进行系列采血。采用非房室方法测定药代动力学参数。通过光透射聚集法测量的血小板对胶原的聚集，以最大血小板聚集率表示。
32名受试者完成了研究。CR沙格雷酯迅速上升，在1.25小时达到Cmax（IR沙格雷酯为1.00小时），并以3.59小时的t1/2下降（IR沙格雷酯为1.12小时）。IR和CR制剂之间AUCτ和Cmax,ss几何平均比的90%置信区间分别为1.18至1.40和0.99至1.29。两种制剂对血小板聚集的抑制程度相似。
与IR沙格雷酯相比，CR沙格雷酯全身暴露量略高，峰浓度相似。两种制剂的药效学和安全性特征相当。
