南方医科大学学报Issue(11)：1616-1620,5.DOI:10.3969/j.issn.1673-4254.2014.11.12
急进高原对普萘洛尔和美托洛尔在大鼠体内药代动力学的影响
Effect of acute exposure to high altitude on pharmacokinetics of propranolol and metoprolol in rats
摘要
Abstract
Objective To study the pharmacokinetics of propranolol and metoprolol in rats after acute exposure to high altitude. Methods Wistar rats were randomly assigned into 4 groups for treatment with intragastric administration of propranolol or metoprolol after acute exposure to high altitude (4010 m) or normal altitude (50 m). Venous blood samples were collected from the rats at different time points after drug administration to determine the drug concentrations in the plasma and plasma ultrafiltrate using liquid chromatography-mass spectrometry (LC-MS/MS). Results The protein binding rate of propranolol was significantly increased but that of metoprolol remained unchanged after acute exposure to high altitude. Compared with the rats exposed to normal altitude, the rats with acute exposure to high altitude showed significant alterations in the pharmacokinetic parameters of the drugs, shown by increased Cmax and AUC, prolonged t1/2 and MRT, and lowered Clz/F of propranolol, and by increased Tmax and prolonged t1/2 and MRT of metoprolol without obvious changes of the parameters of the compartmental model. Conclusion Significant changes in the pharmacokinetics of propranolol and metoprolol occur in rats after acute exposure to high altitude possibly in relation to, apart from the changes in plasma protein binding ratio and blood gas, alterations in metabolic enzyme activities, increased blood viscosity, and species and general conditions of the animals.关键词
普萘洛尔/美托洛尔/急进高原/药代动力学/蛋白结合率Key words
propranolol/metoprolol/acute exposure to high altitude/pharmacokinetics/protein binding引用本文复制引用
张娟红,王荣,谢华,尹强,贾正平,李文斌..急进高原对普萘洛尔和美托洛尔在大鼠体内药代动力学的影响[J].南方医科大学学报,2014,(11):1616-1620,5.基金项目
国家科技部重大资助项目（2008ZXJ09014-010）；全军医药科研“十二五”重点项目（BWS12J012）；全军医药科研“十二五”面上项目 （）
