title: Pharmacokinetic changes of norfloxacin based on expression of MRP2 after acute exposure to high altitude at 4300m.
abstract: BACKGROUND
  This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300m.
  
  
  RESULTS
  The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude. The mRNA and protein expression of MRP2 in high altitude group were higher than plain group in rat small intestine and kidney, while was reduced in rat liver. The AUC, Kaand Cmaxof norfloxacin were significantly reduced in high altitude group (p<0.05). However, the MRT, CL, t1/2and Vd were significantly increased (p<0.05).
  
  
  CONCLUSIONS
  These results indicate that physiological indicators and expression levels of drug transporters MRP2 are changed in responded to high altitude, to severely affect norfloxacin pharmacokinetics. These changes may provide basis and new ideas to adjust the dosage and administration, so as to promote rational drug use in the high altitude.
authors.affiliation: Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China; School of Pharmacy, Lanzhou university, Lanzhou 730000, China.
authors.forename: Bingfeng
authors.initials: B
authors.lastname: Luo
authors.affiliation: Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China; School of Pharmacy, Lanzhou university, Lanzhou 730000, China. Electronic address: wangrong-69@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Gansu Provincial Maternity and Child Care Hospital, Lanzhou 730050, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lu
authors.affiliation: Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China.
authors.forename: Anpeng
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China; School of Pharmacy, Lanzhou university, Lanzhou 730000, China.
authors.forename: Juanhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China. Electronic address: zhengpingjia@163.com.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000531:Altitude; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009643:Norfloxacin / Q000097:blood / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D000900:Anti-Bacterial Agents; D012333:RNA, Messenger; D009643:Norfloxacin
keywords: High altitude; MRP2 expression changes; Norfloxacin; Pharmacokinetics; Physiological changes