高原急性缺氧对大鼠药物转运体PEPT1及阿莫西林药代动力学的影响

发布时间：2018-04-07 17:04

本文选题：急进高原缺氧　切入点：寡肽转运体　出处：《药学学报》2017年11期

【摘要】：寡肽转运体1(PEPT1)与药物疗效、疾病的关联性越来越受到重视,成为提高药物生物利用度很有前途的一种策略,也是临床合理化给药的重要出发点。本研究考察了急进高原缺氧对大鼠PEPT1的表达及其底物药物阿莫西林药代动力学的影响。结果显示,在小肠、肾脏,高原组中PEPT1的mRNA、蛋白表达显著上升36.87%、216.21%、577.8%、535.9%;在肝脏,PEPT1的mRNA表达和蛋白却下降43.90%和84.7%。与平原组相比,高原组阿莫西林的AUC、t_(max)、C_(max)、MRT、t_(1/2)显著性增加312.17%、63.04%、110.93%、67.11%、16.96%,V_d明显降低74.51%。急进高原缺氧后,大鼠药物转运体PEPT1表达会发生明显的变化,从而影响底物阿莫西林的药代动力学。
[Abstract]:Oligopeptide transporter 1 (PEPT1) has been paid more and more attention to its relationship with drug efficacy and disease. It has become a promising strategy to improve the bioavailability of drugs and an important starting point for rationalizing drug delivery.The effects of acute hypoxia on the expression of PEPT1 and the pharmacokinetics of amoxicillin in rats were investigated.The results showed that in the small intestine, kidney and high altitude group, the expression of PEPT1 mRNA and protein increased significantly by 36.87% and 216.21, and the expression of mRNA and protein of PEPT1 decreased by 43.90% and 84.7% in the liver.Compared with plain group, Amoxicillin's Amoxicillin's Amoxicillin's Amoxicillin's Amoxicillin's Amphotocline's Amphotocline's Amphotocline's Amphotocline's Auccinelin (Amoxicillin's Amoxicillin's Amoxicillin / Amoxicillin / Amoxicillin / Amoxicillin / Amoxicillin / Amoxicillin / Amoxicillin / Amoxicillin / Amoxicillin / Amoxicillin /After hypoxia at high altitude, the expression of drug transporter PEPT1 will change obviously, which will affect the pharmacokinetics of amoxicillin substrate.
【作者单位】：兰州军区兰州总医院全军高原损伤防治重点实验室;兰州大学药学院;甘肃省妇幼保健院药剂科;
【基金】：国家科技重大专项(2008ZXJ09014-010) 国家自然科学基金资助项目(81403004,81401552,81673508) 全军后勤科研“十二五”重大项目(AWS14L0005) 全军医学科研“十二五”重点项目(BWS12J012)
【分类号】：R965

【相似文献】