摘要
目的:研究中国健康志愿者单剂量静脉推注90,180,270μg·kg-1依非巴特和连续静脉推注+静脉滴注依非巴特后的药动学行为,并评价依非巴特注射液体内药动学行为和安全性。方法:12名健康志愿者,采用剂量递增的顺序单剂量静脉推注90,180,270μg·kg-1的依非巴特;完成依非巴特单剂量静脉推注药动学试验后,经过1个清洗期,12名受试者随即接受剂量静脉推注依非巴特180μg·kg-1,继而以2.0μg·kg-1·min-1剂量静脉滴注18 h。测定给药后12 h内的血药浓度,用DAS2.0.1软件计算药动学参数。结果:单剂量静脉推注90,180,270μg·kg-1依非巴特注射液后,依非巴特的消除半衰期大约为2.20 h,血浆药物浓度(Cmax)随剂量增加呈线性增加(446.4±86.1)^(1 183.2±320.5)ng·ml-1。另外,曲线下面积(AUC)在90~270μg·kg-1剂量范围内也呈线性增加,AUC0-t:(502.8±113.5)^(1 306.1±278.1)ng·h·ml-1,AUC0-∞:(526.6±110.2)^(1 328.5±277.6)ng·h·ml-1。连续给依非巴特注射液后,依非巴特的tmax为(0.014±0.032)h,t1/2为(2.47±0.64)h,Cmax为(595.7±186.7)ng·ml-1,AUC0-t为(1254.8±514.0)ng·h·ml-1,AUC0-∞为(1 300.9±514.9)ng·h·ml-1。结论:静脉推注依非巴特注射液在90~270μg·kg-1剂量范围内呈线性药动学,Cmax、AUC的升高与剂量成正比。单次静脉推注依非巴特各剂量组间药动学参数均无显著性差异(P>0.05);单次静脉推注依非巴特各剂量组与静脉推注+静脉滴注依非巴特组比较,除t1/2外,其他药动学参数存在显著性差异(P<0.01)。90μg·kg-1剂量组的Cmax、CL和AUC0-t,270μg·kg-1剂量组的CL和AUC0-t,静脉推注+静脉滴注剂量组的CL、Vd和AUC0-t,性别间均有显著性差异(P<0.05或P<0.01)。
OBJECTIVE To characterize the pharmacokinetics of eptifibatide in healthy subjects. METHODS With dose increasing order, twelve healthy subjects were given with single intravenous injection doses of 90,180,270μg·kg-1 eptifibatide. Following a washout period, all subjects accepted by 180μg.kg^-1 eptifibatide dose of intravenous injection of 3 min, and then to 2. 0/μg·kg-1 . min^-1 eptifibatide dose of intravenous drip of 18 h. Plasma concentrations were determined at selected time intervals for 12 hours. The pharmacokinetic parameters were calculated by DAS software. RESULTS The elimination half-life （t1/2） of eptifibatide after i. v 90,180,270 μg-kg-t eptifibatide was about 2. 20 h, the peak plasma concentration （Cmax） in- creased linearly from （446. 4 ± 86. 1） ng.ml^-1 to （1183. 2 ± 320. 5） ng.ml^-1 with the increasing dose. Moreover, the area under the plasma concentration vs time curve increased linearly within the dose range of 90-270μg.kg^-1, AUC0 t from （502. 8± 113.5） ng-h.ml^-1 to （1 306. 1 ± 278. 1） ng.h.ml^-1 , AUC0-∞ from （526. 6 ± 110. 2）-（1 328. 5 ± 277. 6） ng,h.ml^-1 ）. In continuous intravenous infusion dose, tmax was （0. 014 ±0. 032） h, t1/2 was （2. 47 ±0. 64） h,Cmax was （595.7 ± 186. 7） ng-ml^-1 , AUG,, was （1 254.8±514.0） ng.h.ml^-1, AUC0-∞）. was 1 300.9±514.9 ng.h.mL^-1, respectively. CONCLUSION Eptifi- batide exhibits a linear pharmacokinetic profile at the doses in the range of 90--270μg·kg-1. Dose-dependent parameters（Cmax, AUC） increased in an approximately dose-proportional manner from 90- to 270/μg·kg-1. There were no significant differences in the different dose groups of single intravenous injection compared with continuous intravenous infusion dose, except t1/2, other pharmacokinetic parameters had significant difference （P〈0. 01）. Differences in the pharmacokinetic parameters （Cmax, CL, AUG0-t90μg.kg^-1, CL, AUC0-t of 270 μg.kg^-1 and CL, Vd, AUC , of continuous intravenous infusion） between genders were statistically significant（P〈0. 05 or P〈0. 01）.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2014年第14期1151-1156,共6页
Chinese Journal of Hospital Pharmacy
基金
"重大新药创制"科技重大专项十二五第二批项目(编号:2012ZX09303015)
关键词
依非巴特
药动学
剂量相关性
安全性评价
eptifibatide
pharmacokinetics
dose proportionality
safety evaluation
