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Copyright © 2022 Xiao-Bin Zhang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0/

Abstract

Purpose. 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 in vitro and in a rabbit model of obstructive sleep apnea. Materials. Human normal liver (LO-2) cells were exposed to 30 min each of 1%, 1–21%, 21%, and 21–1% O2, 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% (n = 10 per group). Results. The expression of CYP1A2 protein in vitro was significantly reduced in the IH compared with the normoxic cells (0.56 ± 0.11 vs. 1.27 ± 0.17, p<0.001). Aminophylline was more abundant in cell culture supernatants after 48 h of IH than in those under normoxia. The T1/2, AUC0–24 h, and Ke values for aminophylline were significantly higher in the IH group. Conclusion. 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.

Details

Title
Intermittent Hypoxia Inhibits Hepatic CYP1a2 Expression and Delays Aminophylline Metabolism
Author
Xiao-Bin, Zhang 1   VIAFID ORCID Logo  ; Xiao-Yang, Chen 2 ; Kam Yu Chiu 1 ; Xiu-Zhen He 1 ; Wang, Jian-Ming 3 ; Hui-Qing Zeng 1 ; Zeng, Yiming 2   VIAFID ORCID Logo 

 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 
 Department of Pulmonary and Critical Care Medicine, Quanzhou First Affiliated Hospital of Fujian Medical University, Fuzhou, China 
Editor
Qin Yang
Publication year
2022
Publication date
2022
Publisher
John Wiley & Sons, Inc.
ISSN
1741427X
e-ISSN
17414288
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2660754268
Copyright
Copyright © 2022 Xiao-Bin Zhang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0/