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To probe the effects of high-altitude hypoxia environment on the pharmacokinetic parameters of metformin after multiple administration in type 2 diabetes mellitus (T2DM) rats.
Liquid chromatography-mass spectrometry (LC-MS/MS) was used, separation was conducted by a Gemini C18 (75 mm×3 mm, 3 μm) column, the mobile phase was acetonitrile-water-formic acid (85∶15∶0.1, v/v/v), the flow rate was 0.4 mL·min-1, the injection volume was 2 μL, and the internal standard was ranitidine. T2DM rats were randomly divided into plain group and plateau group, and were given continuous gavage once a day for 7 days, and on the 7th day blood samples were collected before administration and at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 h after administration for determination of drug concentration. The DAS 2.0 software was used to simulate and fit the plasma concentration-time data to calculate the pharmacokinetic parameters.
Compared with the rats in the plain group, the peak time (Tmax), clearance rate (CLZ/F) and average residence time (MRT) of metformin were prolonged by 29.03%, 33.25% and 44.98% (P<0.05) in the rats under high-altitude environment, respectively. The AUC increased by 46.22% (P<0.01).
The elimination of metformin is slowed down in T2DM rats after multiple administration under high-altitude hypoxia environment.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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