Abstract
To investigate the effect of high-altitude hypoxia on the pharmacokinetics parameters of gliquidone. 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. 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 P<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 vs. 2.13±0.06, t=11.57, P<0.01). 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.
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More From: Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences
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