Pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology

Pharmacol Res Perspect. 2019 Jul 12;7(4):e00496. doi: 10.1002/prp2.496. eCollection 2019 Aug.


The aim of this study was to evaluate the pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology by reviewing single-dose and steady-state pharmacokinetic studies from the literature. PubMed was searched for pharmacokinetic studies of beta-adrenergic blocking agents, both single-dose and steady-state studies. The studies included reported maximum plasma concentration (Cmax) and/or area under the concentration curve (AUC). The coefficient of variation (CV%) was calculated for all studies, and a CV% <40% was considered low or moderate variability, and a CV% >40% was considered high variability. The Cmax and AUC were reported a total of 672 times in 192 papers. Based on AUC, metoprolol, propranolol, carvedilol, and nebivolol showed high pharmacokinetic variability (highest first), whereas bisoprolol, atenolol, sotalol, labetalol, nadolol, and pindolol showed low to moderate variability (lowest first). We have shown a high interindividual pharmacokinetic variability that varies markedly in different beta-adrenergic blocking agents; the extreme being steady state ratios as high as 30 in metoprolol. A more personalized approach to the medical treatment of patients may be obtained by combining known pharmacokinetic information about variability, pharmaco-genetics and -dynamics, and patient characteristics, to avoid adverse events or lack of treatment effect.

Keywords: Pharmacokinetics; beta‐adrenergic blocking agents; metoprolol; personalized medicine; pharmacology; propranolol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Carvedilol / administration & dosage
  • Carvedilol / pharmacokinetics
  • Healthy Volunteers
  • Humans
  • Male
  • Metoprolol / administration & dosage
  • Metoprolol / pharmacokinetics
  • Propranolol / administration & dosage
  • Propranolol / pharmacokinetics


  • Adrenergic beta-Antagonists
  • Carvedilol
  • Propranolol
  • Metoprolol