title: The Pharmacokinetic Interaction Study between Carvedilol and Bupropion in Rats.
abstract: OBJECTIVE
  The effects of multiple-dose bupropion on the pharmacokinetics of single-dose carvedilol were investigated in order to evaluate this possible drug-drug interaction.
  
  
  METHODS
  A preclinical study was conducted among white male Wistar rats. Each rat was cannulated on the femoral vein prior to being connected to BASi Culex ABC®. During the reference period, each rat received an intravenous and an oral dose of 3.57 mg/kg body weight (b.w.) carvedilol, at 2 days distance. After 5 days of pretreatment with 21.42 mg/kg b.w. bupropion (by oral route, twice a day - given in order to reach the steady state), during the sixth day, 3.57 mg/kg b.w. carvedilol and 21.42 mg/kg b.w. bupropion were orally co-administrated (test period). After each administration of carvedilol, several samples of 200 µL blood were collected. The pharmacokinetic parameters of carvedilol were analyzed by the noncompartmental method.
  
  
  RESULTS
  The 5 days pretreatment with bupropion increased the exposure to carvedilol in rats by 180%, considering the modifications observed in the area under the curve of carvedilol. Carvedilol was shown to have higher plasma concentrations, delay in maximum concentration, and a prolonged half-life, after being pretreated with bupropion.
  
  
  CONCLUSIONS
  The administration of multiple-dose bupropion influences the pharmacokinetics of carvedilol (single oral dose) in rats.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hațieganu", Faculty of Medicine, Cluj-Napoca, Romania.
authors.forename: Maria Bianca
authors.initials: MB
authors.lastname: Abrudan
authors.forename: Dana Maria
authors.initials: DM
authors.lastname: Muntean
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Gheldiu
authors.forename: Maria Adriana
authors.initials: MA
authors.lastname: Neag
authors.forename: Laurian
authors.initials: L
authors.lastname: Vlase
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D016642:Bupropion / Q000493:pharmacokinetics*; D002227:Carbazoles / Q000493:pharmacokinetics*; D000077261:Carvedilol; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics*; D004347:Drug Interactions / Q000502:physiology; D008297:Male; D011412:Propanolamines / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D018765:Dopamine Uptake Inhibitors; D011412:Propanolamines; D016642:Bupropion; D000077261:Carvedilol