兰索拉唑片的人体药动学和生物等效性研究

Pharmacokinetics and Bioequivalence Study of Lansoprazole Tablets in Chinese Healthy Volunteers

关键词:  兰索拉唑  药动学  生物等效性  高效液相色谱法

Key words:  lansoprazole  pharmacokinetics  bioequivalence  HPLC

摘要:

目的建立HPLC测定人血浆中兰索拉唑浓度，评价兰索拉唑片(受试制剂)与兰索拉唑口崩片(参比制剂)的人体生物等效性。方法20名男性健康受试者采用双周期交叉试验，单剂量口服兰索拉唑片和口崩片各30 mg，采集到的血浆样品加入奥美拉唑为内标，碱化后经乙醚-二氯甲烷提取，进行测定。色谱柱为ODS C18柱(150 mm × 4.6 mm，5 μm)；流动相：甲醇-乙腈-水(15∶28∶57 )；检测波长：285 nm，测定血浆中兰索拉唑浓度，应用DAS 2.0.1软件计算主要药代动力学参数，并进行两种制剂的生物等效性评价。结果受试制剂与参比制剂的主要药代动力学参数：Tmax分别为(1.8 ± 0.5)和(1.9 ± 0.5)h；Cmax分别为(1 144 ± 240.8)和(1 162 ± 267.4)ng·mL-1；t1/2分别为(1.4 ± 0.3)和(1.4 ± 0.3)h；AUC0～12分别为(3 258 ± 1 222)和(3 055 ± 1 151)ng·h·mL-1；AUC0-∞分别为(3 341 ± 1 251)和(3 135 ± 1 182)ng·h·mL-1，以AUC0～12计算，与参比制剂相比受试制剂兰索拉唑的相对生物利用度为(108.7±21.6)%(n=20)。结论两种兰索拉唑制剂具有生物等效性。

Abstract:

OBJECTIVE To establish an HPLC method for the determination of lansoprazole in human plasma to evaluate the bioequivalence of lansoprazole tablets and orally disintegrating tablets. METHODS Twenty volunteers were randomly divided into two groups(test and reference)，with double cross over design, single oral dose of lansoprazole at the dose of 30 mg of test tablets and reference orally disintegrating tablets were delivered, respectively. After adding omeprazole, the internal standard, and 200 μL of 0.1 mol·L-1 Na2CO3 solution, the plasma samples were extracted with diethyl ether-dichloromethane and separated on an ODS C18 column(150 mm × 4.6 mm, 5 μm). The mobile phase was methanol-acetonitrile-water (15∶28∶57) and detected at 285 nm. RESULTS The pharmacokinetic parameters of test tablets and reference orally disintegrating tablets were as follows: Tmax were (1.8 ± 0.5) and (1.9 ± 0.5) h; Cmax were (1 144 ± 240.8) and (1 162 ± 267.4) ng·mL-1; t1/2 were (1.4 ± 0.3) and (1.4 ± 0.3) h; AUC0～12 were (3 258 ± 1 222) and (3 055 ± 1 151) ng·h·mL-1; AUC0-∞ were (3 341 ± 1251) and (3 135 ± 1 182) ng·h·mL-1, respectively．The relative bioavalibility of lansoprazole tablets was (108.7 ± 21.6)% (n=20). CONCLUSION The statistical analysis showed that the test and reference preparation were bioequivalent.