单次静滴法舒地尔的药动学  

The Investigation on Pharmacokinetics of Fasudil After a Single Dose Intravenous infusion

作　　者：韩敏[1] 陈华英[1] 林阳[1] 周子杰[1] 王力峰[1] 白梅[1] 李静[1] 汪柯[1] 

机构地区：[1]首都医科大学附属北京安贞医院,北京100029

出　　处：《中国药学杂志》2011年第4期292-296,共5页Chinese Pharmaceutical Journal

摘　　要：目的研究中国健康人单次静滴法舒地尔后法舒地尔及其活性代谢物羟基法舒地尔在体内的药动学特征。方法 12例中国健康成年受试者自身对照交叉设计、单次静脉滴注试验药物甲磺酸法舒地尔和对照药物盐酸法舒地尔,用HPLC-MS/MS方法测定用药后不同时间法舒地尔和羟基法舒地尔的血浆、尿液内浓度,用药动学软件DAS2.1.1进行数据处理。结果法舒地尔在人体内的分布符合一室模型,静滴甲磺酸法舒地尔和盐酸法舒地尔后法舒地尔的主要药动学参数如下:ρmax分别为(200±46)和(188±52)μg.L-1;t1/2分别为(0.398±0.130)和(0.335±0.087)h;AUC0-t分别为(58.7±16.1)和(69.0±30.2)μg.h.L-1;24 h尿药回收率为(5.43±2.66)%和(5.29±2.10)%。2种制剂的原药和代谢物的血药浓度-时间曲线基本一致,药动学参数差异无统计学意义。结论甲磺酸法舒地尔与盐酸法舒地尔的人体药动学过程相似,与文献报道也相近。OBJECTIVE To evaluate the pharmacokinetics of fasudil injection after single dose intravenous infusion in Chinese health volunteers. METHODS The plasma and urine samples of 12 healthy volunteers were collected after injecting 35 mg fasudil mesylate （FM） or 30 mg fasudil hydrochloride （FH）. The concentrations of fasudil and hydroxyfasudil in plasma and urine were determined by a validated HPLC-MS/MS method. Pharmacokinetic parameters were calculated by software DAS2. 1.1. RESULTS Fasudil concentration-time curves of test and reference formulations were discribed by the one compartment open model. The main pharmacokinetic parameters of fasudil were as follow：ρmax（ 200 ± 46 ） and （ 188 ± 52 ）μg·L^-1, tl/2 （ 0. 398 ±0. 130 ） and （ 0. 335 ±0. 087 ） h, AUC0-t（58. 7 ± 16. 1 ） and （69.0 ±30. 2）μg·L^-1, respectively. The 24 h cumulative recovery in urine were （ 5.43 ± 2.66 ） % and （5.29 ± 2.10）% respectively, urinary excretion rates were above 40%. CONCLUSION The pharmacokinetic parameters of FM is similar to FH, and its clinical application can refer to FH （2 -3 times per day, 30 mg once, iv, 30 min）.

关 键 词：法舒地尔 羟基法舒地尔 药动学 

分 类 号：R969.1[医药卫生—药理学]