兰索拉唑分别与铝碳酸镁、莫沙比利合用的大鼠体内药动学研究

Pharmacokinetics of lansoprazole in combination with hydrotalcite or mosapride in rat plasma

目的建立测定大鼠血浆中兰索拉唑的HPLC法，并比较兰索拉唑分别与铝碳酸镁、莫沙比利联合用药的大鼠体内药动学行为。方法18只健康雄性Wistar大鼠随机分为兰索拉唑组、兰索拉唑联合铝碳酸镁组和兰索拉唑联合莫沙比利组，灌胃给药。大鼠血浆样品经甲醇沉淀蛋白处理后进行药物浓度的测定。色谱柱为ODS-C18柱（150mm×4．6mm，5μm）；流动相：甲醇水（53：47）；检测波长：285nm。结果兰索拉唑在50～5000ng·mL^-1线性关系良好，方法回收率为84．0％～90．8％。3种给药方式兰索拉唑的主要药动学参数分别为：tmax：（0．28±0．04）、（2．17±0．26）和（0．28±0．12）h；Cmax：（1939±473．2）、（953±261．0）和（1889±721．9）ng·mL^-1；t1／2：（1．52±0．55）、（1．45±0．40）和（1．67±0．22）h；AUC0-10：（2559±519．5）、（3318±1082）和（3238±1514）ng·h·mL^-1；AUC0-∞：（2729±598．6）、（3498±1149）和（3438±1568）ng·h·mL^-1。经独立样本t检验及非参数检验分析，联用后，铝碳酸镁能明显推迟兰索拉唑达峰时间并降低峰浓度；莫沙比利对兰索拉唑的药动学行为没有显著影响。结论本方法专属性强、准确、简便，可为临床合理用药提供依据。

Objective To establish an HPLC method for comparative study on pharmacokinetics of lansoprazole in combination with hydrotalcite or mosapride in rat plasma. Methods Eighteen Wistar rats were randomly divided into 3 groups for oral administration, respectively. The plasma samples were taken by protein preciptation with methanol and separated on an ODS C18 （150 mm×4.6 mm, 5μm） column with methanol-water （53 ： 47） as the mobile phase. The detective wavelength was 285 nm. Results The calibration curve was linear within 50-5 000 ng·mL^-1 , and the method recovery was within 84.0%-90.8%. The main pharmacokinetic parameters of lansoprazole in the 3 groups were： tmax（0.28 ± 0.04）, （2.17 ± 0.26）, and （0.28 ± 0.12） h; Cmax （1 939 ± 473.2）, （953±261.0）, and （1 889 ± 721.9） ng·mL^-1 t1/2 （1.52 ± 0.55）, （1.45 ± 0.40）, and （1.67 ± 0.22） h; AUC0-10 （2 559 ± 519.5）, （3 318 ± 1082） and （3 238 ± 1 514） ng·h·mL^-1; andAUC0-∞ （2 729±598.6）, （3 498± 1 149）, and （3 438 ± 1 568） ng ·h·mL^-1, respectively. According to independent-sample t test and nonparametric tests, t of lansoprazole was significantly extended, and Cmax was decreased by the co-administration of hydrotalcite; while the pbarmacokinetic parameters of lansoprazole were not affected by the co-administration of mosapride. Conclusion This method is specific, accurate and simple, and can provide reference for the rational use of medicine.