摘要
目的:以泮托拉唑钠肠溶片为对照药,评价左旋泮托拉唑钠肠溶片在健康受试者体内的药动学和药效学。方法:采用随机、开放、阳性药对照试验设计,30名健康受试者分为3组,分别单次和多次给予20 mg、40 mg左旋泮托拉唑钠和40 mg泮托拉唑钠肠溶片,采用LC-MS/MS法测定左旋泮托拉唑血药浓度,计算其药代动力学参数;监测胃内24 h pH值,评价药物的量效关系。结果:单次给药20 mg、40 mg左旋泮托拉唑钠和40 mg泮托拉唑钠肠溶片后左旋泮托拉唑的主要药动学参数C max分别为(1635±410)、(2756±1024)和(1536±615)ng/mL,t1/2分别为(1.41±0.31)、(1.55±0.64)和(1.35±0.22)h,AUC 0-t分别为(3623±1322)、(7383±3785)和(3276±1302)h·ng·mL^-1;多次给药后主要药动学参数:C max分别为(1704±239)、(3297±743)和(1832±557)ng/mL,t1/2分别为(1.41±0.40)、(1.58±0.64)和(1.45±0.22)h,AUC 0~t分别为(3587±1040)、(8189±3399)和(3878±1272)h·ng·mL^-1。单次给药后pH>4.0的时间百分比分别为(32.98±10.7)%、(45.37±9.61)%、和(32.63±14.63)%;多次给药后pH>4.0的时间百分比分别为(45.12±11.97)%、(50.76±10.63)%和(41.67±7.1)%。结论:健康受试者单次和多次给药后左旋泮托拉唑呈线性动力学特征,而40 mg左旋泮托拉唑钠组的药效优于其他剂量组,健康受试者对药物的耐受性良好。
AIM:To evaluate the pharmacokinetics and pharmacodynamics of(S)-pantoprazole sodium enteric-coated tablets in healthy subjects by using pantoprazole sodium enteric-coated tablets as a control drug.METHODS:Thirty healthy Chinese subjects were enrolled in a randomized,open and positive control trial.The subjects were given 20 and 40 mg(S)-pantoprazole sodium enteric-coated tablets and 40 mg pantoprazole sodium enteric-coated tablets,respectively.The concentration of(S)-pantoprazole in the human plasma was determined by LC-MS/MS and the pharmacokinetic parameters were calculated by WinNonlin 6.4 software.The intragastric pH was monitored for 24 hours.The dose-effect relationship of drugs was evaluated.RESULTS:The main pharmacokinetic parameters of(S)-pantoprazole after single administration of 20 and 40 mg(S)-pantoprazole sodium and 40 mg pantoprazole sodium enteric-coated tablets were as follows:The C max were(1635±410),(2756±1024)and(1536±615)ng/mL,the t 1/2 were(1.41±0.31),(1.55±0.64)and(1.35±0.22)h,the AUC 0-t were(3623±1322),(7383±3785)and(3276±1302)h·ng·mL^-1;The main pharmacokinetic parameters of multiple administration were as follows:The C max were(1704±239),(3297±743)and(1832±557)ng/mL,the t1/2 were(1.41±0.40),(1.58±0.64)and(1.45±0.22)h,the AUC0-t were(3587±1040),(8189±3399)and(3878±1272)h·ng·mL^-1.After the treatment,the time of pH>4.0 as a percentage of total time(%)after single administration were(32.98±10.7)%,(45.37±9.61)%and(32.63±14.63)%;and the time of pH>4.0 as a percentage of total time(%)after multiple administration were(45.12±11.97)%,(50.76±10.63)%and(41.67±7.1)%.CONCLUSION:Healthy subjects have linear kinetic characteristics of(S)-pantoprazole after single and multiple administrations,and the 40 mg(S)-pantoprazole sodium group has better efficacy than other dose groups.Healthy subjects were well tolerated.
作者
向荣凤
孙凤军
熊丽蓉
喻明洁
戴青
陈勇川
XIANG Rongfeng;SUN Fengjun;XIONG Lirong;YU Mingjie;DAI Qing;CHEN Yongchuan(Department of Pharmacy,Banan District People's Hospital of Chongqing,Chongqing 401320,China;Department of Pharmacy,First Affiliated Hospital of Army Medical University,Chongqing 400038,China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2020年第8期903-909,共7页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
重庆市社会事业与民生保障科技创新专项(cstc2017shmsA130043)。
关键词
左旋泮托拉唑
泮托拉唑
药动学
药效学
(S)-pantoprazole((S)-PPZ)
pantoprazole(PPZ)
pharmacokinetics
pharmacodynamics
