富马酸替诺福韦二吡呋酯片的人体生物等效性

发布时间：2018-06-22 04:52

本文选题：替诺福韦 + 生物等效性　；参考：《中国新药杂志》2017年16期

【摘要】：目的:评价富马酸替诺福韦二吡呋酯片在健康人体空腹/餐后状态下生物等效性试验研究。方法:采用随机、开放、两周期、两交叉试验设计,26例男性健康受试者随机分成2组,分别空腹/餐后口服受试制剂或参比制剂300 mg,0~72 h间隔采集血样。以液相色谱串联质谱法(LC-MS/MS)法测定血浆替诺福韦浓度,用Win Nonlin软件计算药动学参数。结果:建立的LC-MS/MS法在1.00~600 ng·mL~(-1)范围内线性关系良好,最低定量限为1.00 ng·mL~(-1),批内及批间精密度(RSD)均小于15%。空腹口服受试和参比制剂后,血浆中替诺福韦的主要药动学参数如下:受试制剂和参比制剂的Tmax分别为(0.5±2)和(0.5±1.5)h,Cmax分别为(291.83±66.29)和(321.22±74.65)ng·mL~(-1),t1/2分别为(19.98±2.27)和(21.00±2.93)h,AUC0~72h分别为(2 404.73±532.72)和(2 522.65±567.08)h·ng·mL~(-1)。餐后口服受试和参比制剂后,受试制剂和参比制剂的Tmax分别为(0.75±5)和(1±8)h,Cmax分别为(261.31±101.27)和(292.22±122.67)ng·mL~(-1),t1/2分别为(19.38±2.39)和(19.44±2.26)h,AUC0~72h分别为(3 043.16±731.12)和(3 147.96±930.67)h·ng·mL~(-1)。结论:建立的LC-MS/MS法准确可靠,富马酸替诺福韦二吡呋酯片2种制剂具有人体生物等效性。
[Abstract]:Aim: to evaluate the bioequivalence of tenofovir fumarate dipyrifuroxime tablets in healthy volunteers at fasting / postprandial status. Methods: Twenty-six male healthy subjects were randomly divided into two groups. Blood samples were collected from fasting / postprandial oral trial preparation or reference preparation at intervals of 300 mg / 0 ~ 72 h. The plasma tenofovir concentration was determined by liquid chromatography-tandem mass spectrometry (LC-MS / MS), and the pharmacokinetic parameters were calculated by win Nonlin software. Results: the established LC-MS / MS method had a good linear relationship in the range of 1.00 渭 m ~ (-1) ng mL ~ (-1). The lowest quantitative limit was 1.00 ng mL ~ (-1), and the precision (RSD) was less than 15ng / mL ~ (-1). The main pharmacokinetic parameters of tenofovir were (291.83 卤66.29) ng / t ~ (-1) and (321.22 卤74.65) ng / mL ~ (-1), respectively (291.83 卤66.29) and (321.22 卤74.65) ng / mL ~ (-1), respectively. The main pharmacokinetic parameters of tenofovir in plasma were (2 404.73 卤532.72) and (2 522.65 卤567.08) h ng mL ~ (-1) for 72 h, respectively. The Tmax of the tested and reference preparations were (261.31 卤101.27) and (292.22 卤122.67) ng mL-1 / 2 respectively (19.38 卤2.39) and (19.44 卤2.26) hAUC0h 72 h, (3 043.16 卤731.12) and (3 147.96 卤930.67) h ng mL ~ (-1), respectively. Conclusion: the established LC-MS / MS method is accurate and reliable. The two preparations of tenofovir fumarate dipyrifuroxime tablets are bioequivalent in human.
【作者单位】：吉林大学第一医院;上海药明康德新药开发有限公司;正大天晴药业集团股份有限公司;
【分类号】：R969

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