title: The Effect of Apatinib on the Metabolism of Carvedilol Both in vitro and in vivo.
abstract: BACKGROUND
  In light of the growing number of cancer survivors, the incidence of cardiovascular complications in these patients had also increased, while the effect of apatinib on the pharmacokinetic of cardioprotective drug (carvedilol) in rats or human is still unknown. The present work was to study the impact of apatinib on the metabolism of carvedilol both in vitro and vivo.
  
  
  METHODS
  A specific and sensitive ultra-performance liquid-chromatography tandem mass spectrometry method was applied to determine the concentration of carvedilol and its metabolites (4'-hydroxyphenyl carvedilol [4'-HPC], 5'-hydroxyphenyl carvedilol [5'-HPC] and o-desmethyl carvedilol [o-DMC]).
  
  
  RESULTS
  The inhibition ratios in human liver microsomes were 10.28, 10.89 and 5.94% for 4'-HPC, 5'-HPC and o-DMC, respectively, while in rat liver microsomes, they were 3.22, 1.58 and 1.81%, respectively. The data in vitro of rat microsomes were consistent with the data in vivo that the inhibition of 4'-HPC and 5'-HPC formation was higher than the control group.
  
  
  CONCLUSIONS
  Our study showed that apatinib could significantly inhibit the formation of carvedilol metabolites both in human and rat liver microsomes. It is recommended that the effect of apatinib on the metabolism of carvedilol should be noted and carvedilol plasma concentration should be monitored.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lin
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Junwei
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Wang
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Hu
authors.forename: Xinshe
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002227:Carbazoles / Q000493:pharmacokinetics*; D000077261:Carvedilol; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000378:metabolism; D011412:Propanolamines / Q000493:pharmacokinetics*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D011725:Pyridines; D000077261:Carvedilol; C553458:apatinib