高原环境对醋甲唑胺在大鼠体内药代动力学的影响

Pharmacokinetics of Methazolamide in Rats at High Altitude

目的高原环境下醋甲唑胺在大鼠体内药代动力学特征研究。方法 Wistar大鼠于平原地区(～50 m)禁食12 h后将0.0049 g(约含醋甲唑胺0.476 mg)醋甲唑胺片剂灌胃给药,1周清洗期后急进高原(～4100 m),灌胃给药。平原组及急进高原组于给药前及给药后0.083、0.25、0.5、0.75、1、1.5、2、4、6、8、12、24 h由眼眶后静脉丛取血,采用LC-MS/MS方法测定血药浓度。结果醋甲唑胺急进高原组与平原组相比部分药代动力学参数发生显著变化,与高原组相比半衰期从(6.72±0.41)h减小到(2.61±0.72)h,体内平均驻留时间缩短,峰浓度增大。结论急进高原后,醋甲唑胺在大鼠体内的代谢发生显著变化,本研究结果为平原和急进高原后临床合理应用醋甲唑胺提供参考依据。

Objective To investigate the pharmacokinetics of methazolamide in rats after acute exposure to high altitude.Methods Methazolamide tablets of 0.0049 g were intragastrically administered to rats in low altitude（~50 m） and exposure to high altitude（~4100 m） groups.Blood samples were collected from veins of eye sockets into heparinized centrifuge tubes at 0,0.083,0.25,0.5,0.75,1,1.5,2,4,6,8,12 and 24 h after administration.Plasma concentration of methazolamide was determined by LC-MS/MS.Results Pharmacokinetic parameters of methazolamide at low altitude were significantly different from those of acute exposure to high altitude.Comparison of the t1/2 obtained in plasma in the two groups found a decrease from（6.725±0.406） to（2.61±0.715） h after acute exposure to high altitude.The MRT was lower than in the low-altitude group.Cmax was significantly higher in the acute-exposure-to-high-altitude group than in the low altitude group.Conclusion This study has found significant changes in the metabolism of methazolamide in rats after acute exposure to high altitude,which could be of therapeutic importance.This finding may provide some references for clinical rational use of methazolamide at low altitude and after acute exposure to high altitude.