title: [Effect of acute exposure to high altitude on pharmacokinetics of propranolol and metoprolol in rats].
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Plateau Environmental Damage Control of PLA, Lanzhou General Hospital of Lanzhou Command, Lanzhou 730050, China. E-mail: lzzyzhang@126.com.
authors.forename: Juanhong
authors.initials: J
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yin
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
mesh_terms: D000531:Altitude; D000818:Animals; D002853:Chromatography, Liquid; D008790:Metoprolol / Q000493:pharmacokinetics*; D011433:Propranolol / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry
chemical_list: D011433:Propranolol; D008790:Metoprolol