高原环境对阿莫西林药代参数的影响研究

目的探讨急进高原后大鼠体内阿莫西林药代动力学参数的变化。方法Wistar大鼠于平原地区和急进高原后灌胃给药，分别于给药前（0h）及给药后0．33、0．66、1、1．5、2、3、4、6、8、12、24h采血，采用LC—MS／MS方法测定血药浓度，并分别计算蛋白结合率和药代动力学参数。结果急进高原组血浆蛋白结合率（45．oo％）与平原组血浆蛋白结合率（36．31％）相比显著升高，药一时曲线下面积从（11616．40±1071．92）μg·L^-1·h增大到（47879．24±9417．18）μg·L^-1·h，急进高原后体内平均驻留时间延长，峰浓度增大，清除率降低。结论统计学分析结果显示急进高原后，阿莫西林在大鼠体内药代动力学参数发生显著变化，为进一步研究人体药代动力学提供实验基础和参考依据。

Effects of Aminophylline on the Pharmacokinetic Parameters at High Altitude

Objective To study the changes of pharmacokinetic parameters of aminophylline in rats after acute exposure to high altitude. Methods Blood samples were collected at 0, 0.33, 0.66, 1, 1.5, 2, 3,4, 6, 8, 12, and 24 hours after aminophylline was intragastrically administered to rats at low altitude and after exposure to high alti-tude. The plasma concentration of aminophylline was determined by LC-MS/MS. Results Protein binding was higher in the acute exposure to high altitude（45.00% ） group than in the low altitude group （36.31%）. AUC obtained in plasma increased from （11 616.40 ± 1071.92） μg·L^-1·h to （47 879. 243 ±9417. 176） μg·L^-1·h after acute expo- sure to high altitude. MRT was prolonged and Clz/F was lower in the low altitude group. C max was significantly higher in the acute exposure to high altitude group than in the low altitude group. Conclusion Pharmacokinetic parameters of aminophylline at low altitude were significantly different from those at high altitude. This finding may provide valuable references for study of human pharmacokinetics under hypoxiac environments at high altitude.