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.