Intermittent Hypoxia Inhibits Hepatic CYP1a2 Expression and Delays Aminophylline Metabolism

Xiao-Bin Zhang; Xiao-Yang Chen; Kam Yu Chiu; Xiu-Zhen He; Jian-Ming Wang; Hui-Qing Zeng; Yiming Zeng

doi:10.1155/2022/2782702

Intermittent Hypoxia Inhibits Hepatic CYP1a2 Expression and Delays Aminophylline Metabolism

Evid Based Complement Alternat Med. 2022 Apr 29:2022:2782702. doi: 10.1155/2022/2782702. eCollection 2022.

Authors

Xiao-Bin Zhang¹, Xiao-Yang Chen², Kam Yu Chiu¹, Xiu-Zhen He¹, Jian-Ming Wang³, Hui-Qing Zeng¹, Yiming Zeng²

Affiliations

¹ 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.
² 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.
³ Department of Pulmonary and Critical Care Medicine, Quanzhou First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

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).

Result: s. 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 T _1/2, AUC_{0-24 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.