比较空腹及餐后雷贝拉唑钠肠溶微丸型胶囊的人体生物利用度

发布时间：2019-03-27 10:39

【摘要】：目的:评价空腹和餐后两种状态下口服雷贝拉唑钠肠溶微丸型胶囊的人体生物利用度。方法:22位健康志愿受试者随机分成2组,每组11人,分别空腹或餐后口服给予雷贝拉唑钠肠溶微丸型胶囊或雷贝拉唑钠肠溶片各20 mg,7 d清洗后交叉给药。采用高效液相色谱-串联质谱(HPLC/MS/MS)法测定血浆中雷贝拉唑的血药浓度。结果:空腹口服雷贝拉唑钠肠溶微丸型胶囊与雷贝拉唑钠肠溶片的主要药动学参数如下:t1/2分别为(2.75±1.14)h和(2.57±1.03)h;Tmax(2.57±1.04)h和(3.14±1.09)h;Cmax分别为(372.55±169.10)ng·ml-1和(386.35±174.14)ng·ml-1;AUC0→t分别为(955.98±586.10)ng·h·ml-1和(918.84±445.69)ng·h·ml-1;AUC0→∞(978.14±610.44)ng·h·ml-1和(946.6±473.30)ng·h·ml-1。MRT0→t分别为(3.85±1.11)h和(4.59±1.28)h;MRT0→∞分别为(4.12±1.26)h和(4.92±1.56)h;Vd分别为(100.38±51.26)L·kg-1和(60.81±61.20)L·kg-1。空腹状态下给药的相对生物利用度F为(113.2±59.6)%。餐后口服雷贝拉唑钠肠溶微丸型胶囊与雷贝拉唑钠肠溶片的主要药动学参数如下:t1/2分别为(2.47±0.69)h和(1.94±0.65)h;Tmax(3.27±0.80)h和(4.50±1.13)h;Cmax分别为(404.00±134.38)ng·ml-1和(410.14±126.98)ng·ml-1;AUC0→t分别为(969.66±372.63)ng·h·ml-1和(998.71±443.56)ng·h·ml-1;AUC0→∞分别为(984.97±385.42)ng·h·ml-1和(1 010.56±455.27)ng·h·ml-1;MRT0→t分别为(4.30±0.97)h和(5.50±1.14)h;MRT0→∞分别为(4.50±1.16)h和(5.62±1.19)h;Vd分别为(84.40±42.11)L·kg-1和(67.72±41.67)L·kg-1。餐后给药的相对生物利用度F为(118.1±94.1)%。统计学检验结果表明空腹及餐后给药两制剂间具有生物等效性。试验药组的Tmax在空腹状态下相比参比药组略快,但无显著性差异(P0.05),而在餐后状态下,试验药组Tmax更快,且有显著性差异(P0.05)。空腹及餐后两种状态下试验药组Vd较参比药Vd均有显著性差异(P0.05)。结论:空腹及餐后两种状态下口服雷贝拉唑钠肠溶微丸型胶囊其弥散程度较高、释放药物较快、吸收迅速,用餐对药物的释放及生物利用度的影响较小。
[Abstract]:Objective: To evaluate the bioavailabilities of the enteric micropill type capsule of the oral rebelline sodium enteric-coated capsule in both the fasting and the postprandial state. Methods: Twenty-two healthy volunteers were randomly divided into two groups,11 in each group. After fasting or meal,20 mg and 7 d of the enteric-coated micro-pill or the enteric coated tablets of the rebeella sodium enteric-coated tablets were administered orally, and then they were cross-administered after 7 days. Plasma concentration of Bella in plasma was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/ MS/ MS). Results: The main pharmacokinetic parameters were as follows: t1/2 was (2.75-1.14) h and (2.57-1.03) h, Tmax (2.57-1.04) h and (3.14-1.09) h, respectively. The Cmax values were (372.55-169.10) ng 路 ml-1 and (386.35-174.14) ng 路 ml-1; AUC0-tt was (955.98-586.10) ng 路 h 路 ml-1 and (918.84-445.69) ng 路 h 路 ml-1, respectively; The values of AUC0-1 (978.14-610.44) ng 路 h 路 ml-1 and (946.6-473.30) ng 路 h 路 ml-1. MRT0-t were (3.85-1.11) h and (4.59-1.28) h, respectively; and the MRT0-type was (4.12-1.26) h and (4.92-1.56) h, respectively; and Vd was (100.38-51.26) L 路 kg-1 and (60.81-61.20) L 路 kg-1, respectively. The relative bioavailability of the administration was (113.2, 59.6)% in the fasted state. The main pharmacokinetic parameters were as follows: (2.47-0.69) h, (1.94-0.65) h, Tmax (3.27-0.80) h and (4.50-1.13) h, respectively (404.00-134.38) ng 路 ml-1 and (410.14-126.98) ng 路 ml-1, respectively. The AUC0-acclit was (969.66, 372.63) ng 路 h 路 ml-1 and (998.71-443.56) ng 路 h 路 ml-1; and the AUC0-equivalent was (984.97-385.42) ng 路 h 路 ml-1 and (1 010.56-455.27) ng 路 h 路 ml-1; and the MRT0-t was (4.30-0.97) h and (5.50-1.14) h, respectively; The values of MRT0 were (4.50, 1.16) h and (5.62, 1.19) h, respectively (84.40 and 42.11) L 路 kg-1 and (67.72-41.67) L 路 kg-1, respectively. The relative bioavailability of the post-meal administration F was (118.1-94.1)%. The results of the statistical test showed that the two preparations were bioequivalence between the two preparations. The Tmax of the test group was slightly faster in the fasting state than in the reference group, but there was no significant difference (P0.05). In the fed state, the Tmax of the test group was faster and there was a significant difference (P0.05). There was a significant difference between the Vd of the test group and the reference drug (Vd) in both the fasting and the postprandial state (P0.05). Conclusion: In the two states of fasting and after-meal, the oral rebellate sodium enteric micropill type capsule has a high degree of dispersion, rapid release of the drug, rapid absorption, and less effect on the release and bioavailability of the drug.
【作者单位】：华中科技大学同济医学院附属协和医院临床药学研究室;
【分类号】：R969.1

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