急进4010米高原对呋塞米药代动力学参数的影响

Effects on the pharmacokinetics of furosemide after acute exposure to high altitude at 4010 meters in rats

高原环境具有低氧、低气压、寒冷、强紫外线等特点,其中缺氧是高原环境中影响生命活动的主要因素,机体从平原地区急进高原后,氧分压迅速地降低会导致机体的血氧饱和度快速降低以及组织缺氧,从而导致机体发生一系列生理和病理性变化,机体的这些变化将在很大程度上影响药物的血药浓度、半衰期、清除率等药代动力学参数，如果不调整药物的用法和用量，将严重影响药物的疗效和毒副作用。

The paper is to report the pharmacokinetics of furosemide in rats living at plain area and high altitude. After intragastric administration of furosemide （2.87 mg.kg-1）, serial blood samples （0.5 mL） were collected by retro-orbital puncture at 0, 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h, samples were determined by LC-MS/MS, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters. The main pharmacokinetic parameters： area under curve （AUC）, mean residence time （MRT）, the biological half-life （t1/2） and the peak concentration （Cmax） of furosemide, were significantly increased at high altitude, the time to reach peak concentration （tmax） and clearance （CL） was significantly decreased. This study found significant changes on the pharmacokinetics of furosemide under the special environment of high altitude. This finding may provide some references for clinical rational application of furosemide at high altitude.