title: Effect of multiple doses of fimasartan, an angiotensin II receptor antagonist, on the steady-state pharmacokinetics of digoxin in healthy volunteers.
abstract: Fimasartan (BR-A-657) is an angiotensin II receptor antagonist, recently approved as an antihypertensive agent.
  
  
  OBJECTIVE
  This study aimed to investigate whether administration of fimasartan has an effect on the steady-state pharmacokinetics of digoxin.
  
  
  METHODS
  An open-label, two-period, two-treatment, single-sequence, crossover study was conducted in 14 healthy male volunteers. On the first day of each 7-day treatment period, subjects received a loading dose of digoxin 0.5 mg, either alone or together with fimasartan 240 mg in the morning, followed by an additional dose of digoxin 0.25 mg after 6 h. On the subsequent 6 days, digoxin 0.25 mg, either alone or with fimasartan 240 mg was administered once daily. Serial blood samples for pharmacokinetics were collected up to 24 h after the last administration in each period.
  
  
  RESULTS
  The geometric mean ratio and 90% confidence intervals (CI) for the Cmax,ss and AUCτ,ss of digoxin (with/without fimasartan) were 1.307 (1.123 - 1.520) and 1.087 (1.015 - 1.165), respectively. Study medications were well-tolerated without serious adverse events or clinically meaningful changes.
  
  
  CONCLUSIONS
  Coadministration of fimasartan with digoxin does not result in clinically significant changes of digoxin pharmacokinetics at steady-state in healthy subjects.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Seoul, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Yi
authors.forename: J W
authors.initials: JW
authors.lastname: Kim
authors.forename: T-E
authors.initials: TE
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: Y K
authors.initials: YK
authors.lastname: Jun
authors.forename: J
authors.initials: J
authors.lastname: Choi
authors.forename: S H
authors.initials: SH
authors.lastname: Yoon
authors.forename: J-Y
authors.initials: JY
authors.lastname: Cho
authors.forename: S H
authors.initials: SH
authors.lastname: Song
authors.forename: S-G
authors.initials: SG
authors.lastname: Shin
authors.forename: I-J
authors.initials: IJ
authors.lastname: Jang
authors.forename: K-S
authors.initials: KS
authors.lastname: Yu
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology*; D019540:Area Under Curve; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004077:Digoxin / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D008297:Male; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology*; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D002316:Cardiotonic Agents; D011743:Pyrimidines; D013777:Tetrazoles; D004077:Digoxin; C558933:fimasartan