title: Pharmacokinetic comparison of 2 fixed-dose combination tablets of amlodipine and valsartan in healthy male Korean volunteers: a randomized, open-label, 2-period, single-dose, crossover study.
abstract: BACKGROUND
  Amlodipine and valsartan have different mechanisms of action, and it is known that the combination therapy with the 2 drugs increases treatment effects compared with the monotherapy with each drug. A fixed-dose combination (FDC) drug is a formulation including fixed amounts of active drug ingredients combined in a single dosage form that is expected to improve medication compliance.
  
  
  OBJECTIVE
  The goal of this study was to compare the pharmacokinetic profiles of single administration of a newly developed FDC tablet containing amlodipine orotate 10 mg and valsartan 160 mg (test formulation) with the conventional FDC tablet of amlodipine besylate 10 mg and valsartan 160 mg (reference formulation) in healthy male Korean volunteers.
  
  
  METHODS
  This was a randomized, open-label, single-dose, 2-way crossover study. Eligible subjects were between the ages of 20 and 50 years and within 20% of their ideal weight. Each subject received a single dose of the reference and the test formulations, with a 14-day washout period between formulations. Blood samples were collected up to 144 hours after the dose, and pharmacokinetic parameters were determined for amlodipine and valsartan. Adverse events were evaluated based on subject interviews and physical examinations.
  
  
  RESULTS
  Forty-eight of the 50 enrolled subjects completed the study. For both amlodipine and valsartan, the primary pharmacokinetic parameters were included in the range for assumed bioequivalence, yielding 90% CI ratios of 0.9277 to 0.9903 for AUC(0-last) and 0.9357 to 1.0068 for C(max) in amlodipine, and 0.9784 to 1.1817 for AUC(0-last) and 0.9738 to 1.2145 for C(max) in valsartan. Dizziness was the most frequently noted adverse event, occurring in 4 subjects with the test formulation, followed by oropharyngeal pain occurring in 1 subject with the test formulation and 3 subjects with the reference formulation. All other adverse events occurred in <3 subjects.
  
  
  CONCLUSIONS
  These findings suggest that the pharmacokinetics of the newly developed FDC tablet of amlodipine and valsartan did not differ significantly from the conventional FDC tablet in these healthy Korean male subjects. Both formulations were well tolerated, with no serious adverse events observed. ClinicalTrials.gov identifier: NCT01823913.
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yukyung
authors.initials: Y
authors.lastname: Kim
authors.forename: Mijeong
authors.initials: M
authors.lastname: Son
authors.forename: Donghwan
authors.initials: D
authors.lastname: Lee
authors.forename: Hyerang
authors.initials: H
authors.lastname: Roh
authors.forename: Hankil
authors.initials: H
authors.lastname: Son
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Chae
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Bahng
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D044466:Asian People; D018592:Cross-Over Studies; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000068756:Valsartan; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D013607:Tablets; D013777:Tetrazoles; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine
keywords: amlodipine; combination drug; pharmacokinetic; valsartan