急进高原对甲氧氯普胺蛋白结合率及药代动力学参数的影响

Effect of “acute exposure to high altitude” on the protein binding and pharmacokinetics of metoclopramide

目的研究急进高原对甲氧氯普胺在大鼠体内的血浆蛋白结合率及药代动力学参数的影响。方法 Wistar大鼠于平原地区(海拔50 m)禁食12 h后,将0.002 6 g甲氧氯普胺片剂灌胃给药,一周清洗期后急进高原(海拔4 100 m)并灌胃给药。对平原组和急进高原组大鼠于0、0.083、0.25、0.5、0.75、1、1.5、2、4、6、8、12、24 h分别采用眼眶后静脉丛取血,利用高效液相色谱串联质谱法测定血药浓度。结果急进高原对甲氧氯普胺的血浆蛋白结合率无显著影响(P>0.05);与平原组相比,急进高原组平均驻留时间延长(P<0.05),清除率减小(P<0.05),其他统计矩参数的变化无显著性差异(P>0.05)。结论急进高原后,甲氧氯普胺在大鼠体内代谢过程发生明显改变,研究结果可为由平原急进高原后临床合理应用甲氧氯普胺提供参考依据。

Objective To study on the effect of acute exposure to high altitude on the protein binding and pharmacokinetics of metoclopramide.Methods Metoclopramide tablets of 0.002 6 g was intragastrically administered to rats in a low altitude（50 m） and exposure to a high altitude（4 100 m） groups：The rats residing at the low altitude were after the phases of a 1-week washout period exposed to the high altitude.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 hours after administration of the study drug.The blood concentration of metoclopramide was analyzed by HPLC-MS/MS.Results The protein binding rate of methamphetamine manistested no significant effect in the acute exposure to high altitude group compared with the low altitude group.The average dwell time（MRT） was higher and the clearance rate（CL） was lower,compared with the plain group.The other parameters had no significant difference after acute exposure to high altitude.Conclusion This study found significant changes in the disposition of methamphetamine in those rats after acute exposure to high altitude,which may provide some references for rational clinical application of methamphetamine from a low altitude acute exposure to a high altitude.