title: The effect of AST-120 on the single-dose pharmacokinetics of metoprolol extended-release tablets in healthy subjects.
abstract: BACKGROUND
  This was a randomized, open-label, three-way crossover study to assess the effects of AST-120 (an orally administered spherical carbon adsorbent acting in the gastrointestinal tract without systemic circulation) on the single-dose pharmacokinetics of metoprolol in an extended-release formulation (metoprolol ER) in healthy volunteers.
  
  
  METHODS
  A total of 34 subjects were singly administered metoprolol ER alone (A), and metoprolol ER in combination with AST-120 simultaneously (B) and 1 h later (C).
  
  
  RESULTS
  The total exposure was more significantly reduced in both treatments B and C than that in treatment A; the geometric mean ratios of area under the curve extrapolated to infinity (AUC0-∞) for B/A and C/A were reduced by approximately 30% in both treatments B and C. Maximum observed plasma concentration (Cmax) of metoprolol in treatment B significantly decreased, whereas Cmax in treatment C was slightly decreased. AST-120 treatment was unlikely to affect apparent first-order terminal elimination half-life (T1/2) of metoprolol significantly. Reduction in heart rate and blood pressure readings were similar across the treatment periods. Coadministration of AST-120 and metoprolol ER was safe and was well tolerated.
  
  
  CONCLUSIONS
  Because AST-120 reduced gastrointestinal absorption of metoprolol ER, careful monitoring of heart rate and blood pressure is recommended in coadministration of AST-120 with metoprolol ER.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Inoue
authors.forename: Miho
authors.initials: M
authors.lastname: Shimizu
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Arita
authors.forename: Kei
authors.initials: K
authors.lastname: Akimoto
mesh_terms: D000284:Administration, Oral; D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002244:Carbon / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D065569:Gastrointestinal Absorption; D006207:Half-Life; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D013607:Tablets; D053719:Tandem Mass Spectrometry
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D003692:Delayed-Action Preparations; D010087:Oxides; D013607:Tablets; D002244:Carbon; C040896:AST 120; D008790:Metoprolol