Effects of high-altitude environment on pharmacokinetic parameters of gliquidone in rats
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 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).
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
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| Enthalten in: |
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences - 51(2022), 4 vom: 01. Aug., Seite 389-396 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Longji [VerfasserIn] |
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| Links: |
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| Themen: |
C7C2QDD75P |
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| Anmerkungen: |
Date Completed 22.05.2023 Date Revised 28.10.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.3724/zdxbyxb-2022-0129 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357046374 |
|---|
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| 100 | 1 | |a Huang, Longji |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of high-altitude environment on pharmacokinetic parameters of gliquidone in rats |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 22.05.2023 | ||
| 500 | |a Date Revised 28.10.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: To investigate the effect of high-altitude hypoxia on the pharmacokinetics parameters of gliquidone | ||
| 520 | |a 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 | ||
| 520 | |a 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 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CYP2C9 | |
| 650 | 4 | |a Gliquidone | |
| 650 | 4 | |a Hypobaric hypoxia | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 4 | |a Plateau | |
| 650 | 4 | |a Rats | |
| 650 | 4 | |a Ultra-fast liquid chromatography-tandem mass spectrometry | |
| 650 | 7 | |a gliquidone |2 NLM | |
| 650 | 7 | |a C7C2QDD75P |2 NLM | |
| 650 | 7 | |a Cytochrome P-450 CYP2C9 |2 NLM | |
| 650 | 7 | |a EC 1.14.13.- |2 NLM | |
| 700 | 1 | |a Zhang, Xiaojing |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Mu, Hongfang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Wenbin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Rong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences |d 2002 |g 51(2022), 4 vom: 01. Aug., Seite 389-396 |w (DE-627)NLM123207037 |x 1008-9292 |7 nnns |
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