兰索拉唑单次给药后在健康人体内的药动学研究

Pharmacokinetics Study of Single Administration of Lansoprazole in Healthy Volunteers

目的:了解兰索拉唑在健康人体内的药动学过程。方法:12名健康受试者被给予单次剂量的兰索拉唑(15、30、45mg),采用液-质联用(LC-MS/MS)法检测血浆中兰索拉唑的浓度。结果:11名受试者单次静脉滴注注射用兰索拉唑15、30、45mg后,兰索拉唑的药动参数t1/2分别为(1.44±0.19)、(1.56±0.31)、(1.64±0.34)h,cmax分别为(854.8±115)、(1562±276)、(2348±448)ng/ml,tmax分别为(0.56±0.15)、(0.52±0.050)、(0.56±0.084)h,AUC0-12h分别为(1465±438)、(2894±516)、(5208±1112)ng·h/ml,AUC0-∞分别为(1502±434)、(2934±517)、(5264±1139)ng·h/ml,Vd分别为(21.80±4.64)、(23.30±4.02)、(20.64±3.67)L,CL分别为(10.74±2.99)、(10.55±2.06)、(9.02±2.49)L/h,MRT0-12h分别为(1.97±0.31)、(2.02±0.31)、(2.21±0.36)h,MRT0-∞分别为(2.17±0.31)、(2.16±0.34)、(2.32±0.40)h。观察到1名受试者体内有严重的兰索拉唑蓄积。结论:单次静脉滴注低、中、高剂量注射用兰索拉唑后,均具有线性药动学特征。低剂量条件下男、女受试者的兰索拉唑的t1/2存在显著性差异,其他主要药动学参数不存在性别差异。

OBJECTIVE：To investigate the metabolism of lansoprazole in healthy volunteers. METHODS：12 healthy volunteers were given single dose of lansoprazole（15,30,45 mg）,and the plasma concentration of lansoprazole was determined by LC-MS/MS. RESULTS：Phamarcokinetic parameters of lansoprazole in 11 healthy volunteers after given single dose（15,30,45 mg）were as follows：t 1/2 （1.44±0.19）h,（1.56±0.31）h and（1.64±0.34）h;c max （854.8±115）ng/ml,（1 562±276）ng/ml and （2 348±448）ng/ml;t max （0.56±0.15）h,（0.52±0.050）h and（0.56±0.084）h;AUC 0-12 h （1 465±438）ng·h /ml,（2 894±516）ng· h/ml and（5 208±1 112）ng· h /ml;AUC 0-∞ （1 502±434）ng·h/ml,（2 934±517）ng·h /ml and（5 264±1 139）ng· h /ml;Vd （21.80±4.64）L,（23.30±4.02）L and（20.64±3.67）L;CL（10.74±2.99）L/h,（10.55±2.06）L/h and（9.02±2.49）L/h;MRT 0-12 h （1.97±0.31）h,（2.02±0.31）h and（2.21±0.36）h;MRT 0-∞ （2.17±0.31）h,（2.16±0.34）h and（2.32±0.40）h. Severe accumulation of lansoprazole was found in a volunteer. CONCLUSIONS：Single dose of lansoprazole with intravenous dripping at low,medium and high doses are all in line with linear pharmacokinetic characteristics. There are significant difference in t 1/2 of lansoprazole in female and male volunteers at low dose,and there is no gender difference among other pharmacokinetic parameters.