作 者：
郑经成;周连根;瞿颖;仇珍珍;曹长福;赵慧敏;曾振灵
关键词：
贝那普利;贝那普利拉;药代动力学;生物利用度;家猫
摘 要：
研究贝那普利及其代谢物贝那普利拉在家猫体内的药代动力学特征及生物利用度,为国产盐酸贝那普利片在猫临床上的应用提供依据。选用6只健康家猫,采用双周期随机交叉实验设计,猫单剂量(5mg·只-1)静脉注射盐酸贝那普利注射液或口服盐酸贝那普利片,LC-MS/MS法检测猫血浆中贝那普利和贝那普利拉的质量浓度,采用WinNonlin软件非房室模型计算药动学参数。结果显示:贝那普利原型在猫体内的主要药动学参数分别如下:(1)单剂量静注贝那普利后,贝那普利原型的消除半衰期(t1/2)为(1.91±0.37)h,药时曲线下面积(AUC0-∞)为(1 177.19±227.28)h·ng·mL-1,表观分布容积(Vd)为(3.32±0.74)L·kg-1,体清除率(CLB)为(2.38±0.92)L·(h·kg)-1,平均驻留时间(MRT)为(1.91±0.37)h;(2)单剂量口服贝那普利后,贝那普利原型的t1/2为(1.92±0.31)h,AUC0-∞为(624.36±93.15)h·ng·mL-1,达峰时间(Tmax)为(0.54±0.10)h,峰浓度(Cmax)为(565.32±148.33)ng·mL-1,平均吸收时间(MAT)为(0.90±0.64)h,MRT为(2.43±0.54)h,生物利用度(F)为(57.38±18.83)%。代谢物贝那普利拉在猫体内的主要药动学参数分别如下:(1)单剂量静注贝那普利后,代谢物贝那普利拉的t1/2为(2.89±0.66)h,AUC0-∞为(1 595.37±540.37)h·ng·mL-1,Tmax为(0.46±0.10)h,Cmax为(687.11±68.74)ng·mL-1,MRT为(4.17±0.61)h;(2)单剂量口服贝那普利后,代谢物贝那普利拉的t1/2为(2.63±0.19)h,AUC0-∞为(594.61±90.75)h·ng·mL-1,Tmax为(1.17±0.41)h,Cmax为(124.86±25.67)ng·mL-1,MRT为(4.99±0.40)h。盐酸贝那普利片口服给药后在猫体内具有吸收迅速,体内分布广,达峰迅速,中等生物利用度的特点。临床推荐给药方案为5mg·(只·d)-1。
译 名：
Pharmacokinetics and Bioavailability of Benazepril and Its Metabolite Benazeprilat in Cats
作 者：
ZHENG Jing-cheng;ZHOU Lian-gen;QU Ying;QIU Zhen-zhen;CAO Chang-fu;ZHAO Hui-min;ZENG Zhen-ling;National Reference Laboratory of Veterinary Drug Residues,College of Veterinary Medicine,South China Agricultural University;
关键词：
benazepril;;benazeprilat;;pharmacokinetics;;bioavailability;;cats
摘 要：
The pharmacokinetics and bioavailability of the benazepril and its metabolite benazeprilat,were investigated in cats.A single intravenous(i.v.)or oral(p.o.)administration of benazepril hydrochloride tablets at a dosage of 5 mg was performed in six healthy cats according to a two-period crossover design.The concentration of benazepril and benazeprilat was analysed by high-performance liquid chromatography with tandem mass spectrometry detection(LC-MS/MS)using ESI.The pharmacokinetic parameters were calculated by non-compartmental analysis with WinNonlin 5.2.1software.The main pharmacokinetic parameters of benazepril in cats were asfollows:(1)after a single intravenous administration,the elimination half time(t1/2)was 1.91±0.37 h,area under the curve AUC0-∞was 1 177.19±227.28h·ng·mL-1,apparent volume of distribution ±Vd)was 3.32±0.74 L·kg-1,body clearance ±CLB)was 2.38±0.92L·h-1·kg-1,mean residence time±MRT)was 1.91±0.37h;(2)after a single oral administration,t1/2was 1.92±0.31 h,AUC0-∞was 624.36±93.15h·ng·mL-1,peak time(Tmax)was0.54±0.10 h,peak concentration(Cmax)was 565.32±148.33ng·mL-1,MRT was 2.43±0.54 h,mean absorb time(MAT)was 0.90(0.64 h,bioavailability(F)was 57.38±18.83 %.The main pharmacokinetic parameters of benazeprilat in cats were as follows:(1)after a single intravenous administration,t1/2was 2.89±0.66 h,AUC0-∞was 1 595.37±540.37h·ng·mL-1,Tmax was 0.46±0.10 h,Cmaxwas 687.11±68.74ng·mL-1,MRT was 4.17±0.61h;(2)after a single oral administration,t1/2was 2.63±0.19 h,AUC0-∞was 594.61±90.75h·ng·mL-1,Tmaxwas1.17±0.41 h,Cmaxwas 124.86±25.67ng·mL-1,MRT was 4.99±0.40 h.The results of present studies showed that benazepril hydrochloride tablets have characteristics of rapid absorption,extensive distribution and medium bioavailability in cats,and the recommended clinical regimen of benazepril hydrochloride tablets is 5mg per day.
