Pharmacokinetics of Acetaminophen and Metformin Hydrochloride in Rats After Exposure to Simulated High Altitude Hypoxia.
Pharmacokinetics of Acetaminophen and Metformin Hydrochloride in Rats After Exposure to Simulated High Altitude Hypoxia.
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对乙酰氨基酚和盐酸二甲双胍在模拟高原缺氧大鼠体内的药代动力学
DOI：
10.3389/fphar.2021.692349
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发表时间：
2021
影响因子：
5.6
通讯作者：
Li XY
中科院分区：
文献类型：
--
作者：
Zhu JB;Yang JX;Nian YQ;Liu GQ;Duan YB;Bai X;Wang Q;Zhou Y;Wang XJ;Qu N;Li XY
高原缺氧改变了药物的药动学特性，影响了药物的吸收、分布、代谢和排泄。然而，关于解热镇痛药物和心血管系统药物在高海拔地区药代动力学变化的文献很少。本研究旨在评价对乙酰氨基酚和盐酸二甲双胍在模拟高原缺氧条件下大鼠体内的药动学。机械方面，分别采用酶联免疫吸附试验（ELISA）和实时定量聚合酶链式反应（qRT-PCR）检测尿苷二磷酸葡萄糖醛基转移酶1A1 （UGT1A1）和有机阳离子转运蛋白2 （OCT2）的蛋白表达和mRNA表达。与正常缺氧组比较，模拟高原缺氧后大鼠对乙酰氨基酚的t1/2和AUC显著升高，CL/F显著降低。模拟高原缺氧使盐酸二甲双胍t1/2显著升高。缺氧组与常氧组盐酸二甲双胍AUC和CL/F无显著差异。缺氧大鼠UGT1A1和OCT2蛋白及mRNA表达均显著降低。本研究发现模拟高原缺氧后对乙酰氨基酚和盐酸二甲双胍在大鼠体内的药代动力学发生了明显变化，可能是由于UGT1A1和OCT2的表达显著降低所致。综上所述，我们的数据表明，在缺氧暴露下，对乙酰氨基酚和盐酸二甲双胍的药代动力学应该重新检查，并重新评估最佳剂量。
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.
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影响因子：
4.5
作者：
Jiang C;Chen J;Liu F;Luo Y;Xu G;Shen HY;Gao Y;Gao W
通讯作者：
Gao W
影响因子：
9.6
作者：
Dunham-Snary, Kimberly J.;Wu, Danchen;Archer, Stephen L.
通讯作者：
Archer, Stephen L.
影响因子：
3.2
作者：
Li, Xiang-Yang;Gao, Fen;Ge, Ri-Li
通讯作者：
Ge, Ri-Li
影响因子：
2.1
作者：
Li, Xiangyang;Wang, Xuejun;Duan, Yabin
通讯作者：
Duan, Yabin
影响因子：
1.3
作者：
Adak, A.;Maity, C.;Mondal, K. C.
通讯作者：
Mondal, K. C.