Zhang Xiao-Bin, Chen Xiao-Yang, Chiu Kam Yu, He Xiu-Zhen, Wang Jian-Ming, Zeng Hui-Qing, Zeng Yiming
Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Xiamen University, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Siming District, Xiamen, Fujian Province, China.
Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, Second Clinical Medical College of Fujian Medical University, Center of Respiratory Medicine of Fujian Province, China.
Evid Based Complement Alternat Med. 2022 Apr 29;2022:2782702. doi: 10.1155/2022/2782702. eCollection 2022.
In this study, we aimed to determine the effects of intermittent hypoxia (IH) on hepatic cytochrome P450 1A2 (CYP1A2) expression and the pharmacokinetics of CYP1A2-mediated aminophylline and warfarin and in a rabbit model of obstructive sleep apnea.
Human normal liver (LO-2) cells were exposed to 30 min each of 1%, 1-21%, 21%, and 21-1% O, and then, CYP1A2 expression and drug concentrations were analyzed. We compared the pharmacokinetic parameters of drugs administered to normoxic rabbits and those exposed to 10 min of IH during which the oxygen level fluctuated from 21% to 8%-10% ( = 10 per group).
s. The expression of CYP1A2 protein was significantly reduced in the IH compared with the normoxic cells (0.56 ± 0.11 vs. 1.27 ± 0.17, < 0.001). Aminophylline was more abundant in cell culture supernatants after 48 h of IH than in those under normoxia. The , AUC, and Ke values for aminophylline were significantly higher in the IH group.
Intermittent hypoxia inhibits hepatic CYP1A2 expression and delays aminophylline metabolism, suggesting that the impact of IH on the expression of CYP enzymes should be closely monitored in clinical practice.
在本研究中，我们旨在确定间歇性低氧（IH）对阻塞性睡眠呼吸暂停兔模型中肝细胞色素P450 1A2（CYP1A2）表达以及CYP1A2介导的氨茶碱和华法林药代动力学的影响。
将人正常肝（LO-2）细胞暴露于1%、1%-21%、21%和21%-1%氧气环境中各30分钟，然后分析CYP1A2表达和药物浓度。我们比较了给予常氧兔和暴露于10分钟间歇性低氧（氧气水平从21%波动至8%-10%）的兔（每组n = 10）的药物药代动力学参数。
与常氧细胞相比，间歇性低氧组中CYP1A2蛋白表达显著降低（0.56±0.11对1.27±0.17，P<0.001）。间歇性低氧48小时后，细胞培养上清液中的氨茶碱比常氧条件下更丰富。间歇性低氧组中氨茶碱的Cmax、AUC和Ke值显著更高。
间歇性低氧抑制肝脏CYP1A2表达并延迟氨茶碱代谢，提示在临床实践中应密切监测间歇性低氧对CYP酶表达的影响。
