Pharmacokinetics of Acetaminophen and Metformin Hydrochloride in Rats After Exposure to Simulated High Altitude Hypoxia

Frontiers in Pharmacology

Gui-qin Liu¹  Ning Qu²  Xue-jun Wang³  Yang Zhou⁴  Xue Bai⁴  Ya-bin Duan⁴  Qian Wang⁴  Yong-qiong Nian⁵  Jian-xin Yang⁶  Xiang-yang Li⁶  Jun-bo Zhu⁶ 

[1] College of Eco-Environmental Engineering, Qinghai University, Xining, China;Department of Anesthesiology, Qinghai Hospital of Traditional Chinese Medicine, Xining, China;Department of Anesthesiology, Red Cross Hospital of Qinghai, Xining, China;Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China;School of Pharmacy, Qinghai Nationalities University, Xining, China;State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China;

关键词: acetaminophen;    metformin hydrochloride;    high altitude hypoxia;    pharmacokinetics;    UGT1A1;    OCT2;   

DOI  :  10.3389/fphar.2021.692349

来源: DOAJ

【 摘 要 】

The pharmacokinetic characteristics of drugs were altered under high altitude hypoxia, thereby affecting the absorption, distribution, metabolism, and excretion of drug. However, there are few literatures on the pharmacokinetic changes of antipyretic and pain-relieving drugs and cardiovascular system drugs at high altitude. This study aimed to evaluate the pharmacokinetics of acetaminophen and metformin hydrochloride in rats under simulated high altitude hypoxia condition. Mechanically, the protein and mRNA expression of uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) and organic cation transporter 2 (OCT2) were investigated by enzyme linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Compared with the normoxia group, the t1/2 and AUC of acetaminophen were significantly increased, and the CL/F was significantly decreased in rats after exposure to simulated high altitude hypoxia. The t1/2 of metformin hydrochloride was significantly increased by simulated high altitude hypoxia. No significant differences in AUC and CL/F of metformin hydrochloride were observed when comparing the hypoxia group with the normoxia group. The protein and mRNA expression of UGT1A1 and OCT2 were decreased significantly under hypoxia in rats. This study found obvious changes in the pharmacokinetics of acetaminophen and metformin hydrochloride in rats after exposure to simulated high altitude hypoxia, and they might be due to significant decreases in the expressions of UGT1A1 and OCT2. To sum up, our data suggested that the pharmacokinetics of acetaminophen and metformin hydrochloride should be reexamined, and the optimal dose should be reassessed under hypoxia exposure.

【 授权许可】

Unknown