title: A pharmacokinetic and pharmacodynamic comparison of immediate-release metoprolol and extended-release metoprolol CR/XL in patients with suspected acute myocardial infarction: a randomized, open-label study.
abstract: BACKGROUND
  Previous metoprolol studies in myocardial infarction patients were performed with immediate-release (IR) metoprolol. This study aims to evaluate if extended-release metoprolol CR/XL once daily gives a similar β-blockade over 24 h compared to multiple dosing of metoprolol IR.
  
  
  METHODS
  After 2 days of routine metoprolol treatment, 27 patients with suspected acute myocardial infarction were randomized to open-label treatment with metoprolol IR (50 mg four times daily or 100 mg twice daily) or metoprolol CR/XL 200 mg once daily for 3 days.
  
  
  RESULTS
  Metoprolol CR/XL 200 mg once daily gave more pronounced suppression of peak heart rate, with lower peak and less variation in peak to trough plasma levels. There were no differences in AUC between the CR/XL and IR formulations, although the trough plasma metoprolol levels were comparable for metoprolol CR/XL 200 mg once daily and metoprolol IR 50 mg four times daily, but lower for metoprolol IR 100 mg twice daily. Both treatments were well tolerated.
  
  
  CONCLUSIONS
  Metoprolol CR/XL 200 mg once daily showed lower peak and less variation in peak to trough plasma levels compared to multiple dosing of metoprolol IR with the same AUC. This was accompanied by a more uniform β-blockade over time, which was reflected by heart rate, and a more pronounced suppression of peak heart rate with similar tolerability. This suggests metoprolol CR/XL may be used as an alternative to metoprolol IR in patients with myocardial infarction.
authors.affiliation: AstraZeneca R & D, Mölndal, Sweden.
authors.forename: Björn W
authors.initials: BW
authors.lastname: Karlson
authors.forename: Mikael
authors.initials: M
authors.lastname: Dellborg
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Jan
authors.initials: J
authors.lastname: Aberg
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sugg
authors.forename: Johan
authors.initials: J
authors.lastname: Herlitz
mesh_terms: D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D013607:Tablets
chemical_list: D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D013607:Tablets; D008790:Metoprolol