Change of hepatic drug metabolism enzymes in rat depression model with kidney-yang deficiency
10.16438/j.0513-4870.2016-0831
- VernacularTitle:肾阳虚抑郁症模型大鼠的肝脏药物代谢酶活性变化研究
- Author:
Shu-fen HE
1
;
Wen-zheng JU
1
;
Hao-bin HU
2
;
Li-jing ZHU
1
;
Qian ZHANG
1
;
Guo-liang DAI
1
Author Information
1. Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
2. Jiangsu Institute for Food and Drug Control, Nanjing 210008, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
depression;
kidney-yang deficiency;
cocktail probe drug;
LC-MS/MS;
cytochrome P450
- From:
Acta Pharmaceutica Sinica
2017;52(2):258-263
- CountryChina
- Language:Chinese
-
Abstract:
This study was designed to explore the impact of depression on kidney-yang deficiency in rats. Rats were repeatedly injected with hydrocortisone for 21 days to establish the depression model with kidneyyang deficiency. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were used as substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1, and CYP2D2 to test the depression impact on drug metabolism. Plasma concentrations of six CYP450 were determined by LC-MS/MS and used as pharmacokinetic parameters. Consequently, metabolism of theophylline, chlorzoxazone and tolbutamide were accelerated significantly in the model relative to the control (P<0.01), but dextromethorphan, omeprazole and midazolam did not exhibit a significant difference. The present study suggests that depression with kidneyyang deficiency had a strong induction of CYP2E1 and moderate induction of CYP1A2, CYP2C6 in the rat model.
