高原环境对格列喹酮在大鼠体内药代动力学参数的影响。
Effects of high-altitude environment on pharmacokinetic parameters of gliquidone in rats.
出版信息
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2022 Aug 1;51(4):389-396. doi: 10.3724/zdxbyxb-2022-0129.
OBJECTIVE
To investigate the effect of high-altitude hypoxia on the pharmacokinetics parameters of gliquidone.
METHODS
Twelve healthy male Wistar rats were randomly divided into plain group and high-altitude group with 6 rats in each group. Blood samples were collected after intragastric administration of gliquidone (6.3 mg/kg). Ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was used to determine the concentration of gliquidone in rat plasma samples. And the expression of CYP2C9 in rat liver tissues was determined by Western blotting.
RESULTS
Compared with the plain group, the peak concentration of gliquidone in the high-altitude rats was significantly increased, the absorption rate constant was decreased, the elimination rate constant and the absorption half-life were increased, the elimination half-life was shortened, the mean residence time and apparent volume of distribution were decreased (all <0.05). Western blotting showed that the expression of CYP2C9 was significantly up-regulated in the liver tissues of high altitude group rats, compared with the plain group (4.18 ±0.06 . 2.13±0.06, =11.57, 0.01).
CONCLUSION
Under the high-altitude hypoxia environment, the absorption of gliquidone in rats was reduced and the metabolism was accelerated in rats, which may be related to the up-regulation of CYP2C9 expression in liver tissues.
目的
研究高原低氧环境对格列喹酮药代动力学参数的影响。
方法
将 12 只健康雄性 Wistar 大鼠随机分为平原组和高原组，每组 6 只。大鼠灌胃给予格列喹酮（6.3mg/kg）后采集血样。采用超快速液相色谱-串联质谱法（UFLC-MS/MS）测定大鼠血浆中格列喹酮的浓度。采用 Western blot 法测定大鼠肝组织中 CYP2C9 的表达。
结果
与平原组比较，高原组大鼠格列喹酮的峰浓度明显升高，吸收速率常数降低，消除速率常数和吸收半衰期延长，消除半衰期缩短，平均驻留时间和表观分布容积减小（均<0.05）。Western blot 结果显示，高原组大鼠肝组织中 CYP2C9 的表达明显上调，与平原组比较[（4.18±0.06）∶（2.13±0.06），=11.57，0.01]。
结论
在高原低氧环境下，大鼠格列喹酮的吸收减少，代谢加快，这可能与肝组织中 CYP2C9 表达上调有关。
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