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目的:对平原与高原组大鼠体内呋塞米和醋甲唑胺的血浆蛋白结合率差异进行比较。方法:Wistar大鼠于平原地区禁食12 h后分别将呋塞米0.001 7 g、醋甲唑胺0.004 9 g片剂灌胃给药,清洗期后,急进高原灌胃给药。给药后0.66、2、4 h由眼眶后静脉丛取血(呋塞米),醋甲唑胺采血时间点为0.66、2、8 h,采用超滤法测定呋塞米和醋甲唑胺血浆蛋白结合率,LCMS/MS方法测定呋塞米和醋甲唑胺血浓度。结果:急进高原后呋塞米蛋白结合率略有增高,但无显著性差异。而醋甲唑胺组蛋白结合率增高明显,平原组和急进高原组血浆蛋白结合率值分别为(21.52±1.22)%、(73.98±2.09)%。结论:本研究发现急进高原后大鼠体内呋塞米和醋甲唑胺血浆蛋白结合率变化不同,血浆蛋白结合率的变化可能会影响药物药动学特征。
OBJECTIVE: To compare the plasma protein binding rates of furosemide and methazolamide in rats in plain and plateau group. Methods: Wistar rats were fasted with 0.001 7 g of furosemide and 0.004 9 g of metoclopramide respectively after 12-hour fasting in plain area. After washing, they were administered intragastrically to the plateau. 0.66,2,4 h after administration of blood from the retro-orbital venous plexus (furosemide), Methazolamide blood collection time points of 0.66,2,8 h, the determination of furosemide and metforzamide by ultrafiltration Plasma protein binding, LCMS / MS method was used to determine the blood concentration of furosemide and metforzamide. Results: The binding rate of furosemide protein increased slightly after reaching the plateau, but there was no significant difference. However, the binding rate of acetaminophen to histones increased significantly, and the plasma protein binding rates were (21.52 ± 1.22)% and (73.98 ± 2.09)%, respectively. CONCLUSION: In our study, we found that plasma protein binding rate of furosemide and methachlodiazole in rats changed rapidly after acute high altitude, and the change of plasma protein binding rate may affect the pharmacokinetic characteristics of rats.