泮托拉唑钠在大鼠体内药动学研究  

Pharmacokinetics of pantoprazole sodium in rats

作　　者：王欣[1] 谭明芬 黄莉莉[1] 

机构地区：[1]南京大学医学院附属鼓楼医院药剂科,江苏南京210008 [2]连云港市赣榆区畜牧兽医站,江苏连云港222100

出　　处：《现代药物与临床》2016年第8期1141-1145,共5页Drugs & Clinic

基　　金：中华医学会医学教育研究课题资助项目(2012-SY-44)

摘　　要：目的建立HPLC法测定大鼠血浆中泮托拉唑钠对映体,研究泮托拉唑钠在大鼠体内药动学特征。方法血浆用醋酸乙酯提取,以非那西丁为内标,Chiralcel OJ-RH色谱柱（250 mm×4.6 mm,5μm）,流动相为20 mmol/L磷酸二氢钠（含0.01%磷酸）–乙腈（78∶22）,紫外检测波长为288 nm,体积流量为1.0 m L/min,柱温40℃。大鼠尾iv消旋体16 mg/kg,HPLC-UV法测定血浆中左旋和右旋泮托拉唑钠浓度,并采用DAS 2.0软件计算药动学参数。结果左旋泮托拉唑钠、右旋泮托拉唑钠线性范围均为0.156～40.000μg/m L,定量限为0.156μg/m L。泮托拉唑钠左旋体与右旋体的主要药动学参数分别为：Cmax（38.13±3.33）、（40.52±3.69）μg/L;AUC0-τ（1 688.45±302.38）、（1 399.88±376.44）min·μg/m L;AUC0-∞（1710.61±309.40）、（1 417.29±383.21）min·μg/m L;t1/2（30.92±6.41）、（22.37±7.59）h。结论泮托拉唑钠对映体在大鼠体内的药动学存在立体选择性特征,为临床合理应用手性药物泮托拉唑钠提供参考。Objective To establish an HPLC method to determine pantoprazole sodium enantiomers in plasma, and study its pharmacokinetics in rats. Methods Pantoprazole sodium and phenacetin internal standard were extracted by liquid-liquid extraction and separated on Chiralcel OJ-RH column（250 mm × 4.6 mm, 5 μm）, with 20 mmol/L natrium biphosphoricum（containing 0.01% phosphoric acid）- acetonitrile（22∶78） as mobile phase. The column temperature was set at 40 ℃, and the analytical wavelength was 288 nm with flow rate as 1.0 m L/min. Rats were tail iv administered with racemic pantoprazole sodium 16 mg/kg, and L- and D-pantoprazole sodium in plasma were determined by HPLC-UV method. DAS 2.0 software was used to calculate the pharmacokinetic parameters. Results The calibration curve was linear over the concentration range of 0.156 — 40.00 μg/m L with a sensitivity of 0.156 μg/m L as the limit of quantification. Main pharmacokinetic parameters were as following： Cmax for L- and D-pantoprazole sodium were（38.13 ± 3.33） and（40.52 ± 3.69） μg/L; AUC0-τ were（1 688.45 ± 302.38） and（1 399.88 ± 376.44） min·μg/m L; AUC0-∞ were（1 710.61 ± 309.40） and（1 417.29 ± 383.21） min·μg/m L; t1/2 were（30.92 ± 6.41） and（22.37 ± 7.59） min. Conclusion Pharmacokineties of pantoprazole enantiomers has a stereoseleetive character in rats, which provide reference for clinical rational application of chiral drug pantoprazole sodium.

关 键 词：泮托拉唑钠 对映异构体 高效液相色谱 药动学 

分 类 号：R969.1[医药卫生—药理学]