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• 药物研究 • 上一篇    下一篇

复方蒿甲醚片人体药动学及生物等效性研究

丁百莲,王彦君,林长旭   

  1. 沈阳双鼎制药有限公司,沈阳达善医药科技有限公司 辽宁沈阳 110179,沈阳双鼎制药有限公司
  • 收稿日期:2016-03-04 修回日期:2016-03-04 出版日期:2016-06-25 发布日期:2016-06-25

Study on Pharmacokinetics and Bioequivalence of Compound Artemether Tablets

  1. Shuangding Pharmaceutical Co,Ltd,Dasan Medichem (Shenyang) R,Shuangding Pharmaceutical Co,Ltd
  • Received:2016-03-04 Revised:2016-03-04 Online:2016-06-25 Published:2016-06-25

摘要: [摘 要]目的:建立测定人血浆中蒿甲醚、双氢青蒿素和苯芴醇的液相色谱-串联质谱法(LC-MS/MS),对复方蒿甲醚片进行人体生物等效性研究。方法:采用随机、双周期、自身交叉试验设计,受试者单剂量口服受试制剂或参比制剂,并使用Phoenix WinNonlin 6.0数据统计软件计算药代动力学参数,评价复方蒿甲醚片的生物等效性。结果:线性范围为2.0~199.2 ng?mL-1(蒿甲醚),2.0~204.2 ng?mL-1(双氢青蒿素),0.0200~14.9640 μg?mL-1(苯芴醇)。受试制剂与参比制剂蒿甲醚的AUC0-t分别为(193.3?25.5)和(184.3?30.5) ng?h?mL-1;双氢青蒿素的AUC0-t分别为(328.7?103.3)和(320.5?62.1) ng?h?mL-1;苯芴醇的AUC0-t分别为(180.2?70.5)和(173.8?51.4) ng?h?mL-1;以AUC0-t计,受试制剂相对生物利用度蒿甲醚为(106.1?12.9)%,双氢青蒿素的相对生物利用度为(101.2?18.9)%,苯芴醇的相对生物利用度为(103.3?19.7)%。结论:该方法简便、灵敏、准确,适用于复方蒿甲醚片的人体生物等效性研究。统计结果表明受试制剂和参比制剂具有生物等效性。

Abstract: [Abstract]Objective: To develop a liquid chromatographic-mass spectrometric(LC-MS/MS) method for the de-termination of lumefantrine Artemether、dihydroartemisinin、lumefantrine in human plasma and evaluate the bioequivalence of Compound Artemether Tablets. Methods: In a ran-domized,double- period,self-crossover study,subjects received a single oral dose of test or reference formulation. The main pharmacokinetic parameters were calculated by software Phoenix WinNonlin 6.0 and the bioequivalence of two formulations was evaluated.Results:The linear calibration curve was obtained over the con-centration range of 2.0~199.2 ng·mL-1(Artemether)、2.0~204.2ng·mL-1 (dihydroartemisinin), 0.0200~14.964 μg·mL-1(lumefantrine).The main pharmacokinetic parameters of test formulation and reference formulation were as following: AUC0-t were (193.3±25.5) and (184.3± 30.5) ng·h·mL-1 (Artemether), (328.7±103.3) and (320.5±62.1) ng·h·mL-1 (dihydroartemisinin), (180.2±70.5) and 173.8± 51.4) ng·h·mL-1 (lumefantrine); By calculation of AUC 0-t the relative bioavailability of test formulation was (106.1%±12.9%) Artemether, (101.2%±18.9%) dihydroartemisinin, 103.3%±19.7%) lumefantrine. Conclusion: The method was simple,sensitive,accurate and suitable for the bioequivalence study of Compound Artemether Tablets in human.The statistic data showed that the test formulation and reference formulation had the similar rate and extent of absorption,and they were bioequivalent.