替米沙坦与那格列奈在比格犬体内的药动学相互作用  

Pharmacokinetic interactions between telmisartan and nateglinide in Beagle dogs

作　　者：杨小英[1,2] 魏世杰[1,2] 陈和莉[3] 杨付英[3] 党宏万[1,2] 

机构地区：[1]宁夏医科大学总医院药剂科,宁夏银川750004 [2]宁夏医科大学总医院临床药理研究室,宁夏银川750004 [3]宁夏医科大学药学院,宁夏银川750004

出　　处：《中国医院药学杂志》2012年第23期1873-1876,共4页Chinese Journal of Hospital Pharmacy

基　　金：宁夏自然科学基金(编号:NZ08115)

摘　　要：目的:研究那格列奈与替米沙坦联用在犬体内的药动学相互作用。方法:采用自身对照随机交叉的试验方法,将比格犬分为3组,每组3只,分别按试验周期服用替米沙坦、那格列奈、替米沙坦加那格列奈。高效液相色谱-串联质谱(HPLC-MS/MS)法测定不同时间点的血药浓度,计算药动学参数。结果:替米沙坦单用与联用相比,其tmax(h)(1.7±0.4)vs(3.1±0.8)(P<0.05),其余药动学参数变化不大;那格列奈单用与联用相比,其AUC(0-t)(mg.h.L-1)(24.7±3.5)vs(15.2±1.7),AUC(0-∞)(mg.h.L-1)(29.8±4.3)vs(18.1±2.1),Cmax(mg.L-1)(4.4±0.6)vs(3.1±0.4),CL/F(L.kg-1.h-1)(0.43±0.21)vs(0.06±0.02)and V/F(L.kg-1)(2.7±0.9)vs(0.33±0.16)(P<0.05)。结论:替米沙坦与那格列奈联合用药时彼此影响其药动学参数。ORJECTIVE To investigate the pharmacokinetic interactions between telmisartan（TEL） and nateglinide（NAT） in Beagle dogs. METHODS A randomized, 3-treatment, 3-period, 3-sequence crossover study was conducted with 9 healthy adult Beagle dogs divided into 3 groups. Each group was assigned to receive oral TEL , NAT and TEL plus NAT respectively, followed by a 15-day washout period and then administration of the alternate treatment. Plasma samples were collected at fixed time points. The plasma 2-drug concentrations were determined by HPLC-MS/MS. The pharmacokinetic parameters were com puted and analyzed by software program DAS 2. 0. RESULTS Compared with the values obtained when TEL was administered alone, concurrent administration of NAT resulted in a significant increase in TEL tmax （h） （ 1.7 ± 0. 5） vs （3. 1 ± O. 8） （P〈O. 05） whereas its other pharmacokinetic parameters showed no obvious difference. Compared with the values got when NAT was taken alone, coadministration of TEL distinctly altered NAT pharmacokinetic parameters such as AUC（0-t） （mg. h. L 1 ） （24. 7 ± 3.5） vs （15.2±1.7）, AUC（0-∞） （ mg.h.L 1） （29.8±4.3） vs （18.1±2.1）, Cmax（mg·L -1） （4.4±0.6） vs （3.1 ±0.4）,CL/F （L·kg-l·h -1） （0.43±0.21） vs （0.06±0.02） andV/F（L.kg-1） （2. 7±0.9） vs （0. 33±0.16）（P〈0.05）. CONCLUSION There are pharmacokinetic interactions between TEL and NAT in Beagle dogs. This study showed that NAT increased TEL tmax, while TEL decreased NAT AUC,Cmax CL/F and V/F.

关 键 词：替米沙坦 那格列奈 药动学 高效液相色谱-串联质谱法 

分 类 号：R977.15[医药卫生—药品]