Pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology

TY - JOUR

T1 - Pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology

AU - Ågesen, Frederik N

AU - Weeke, Peter E

AU - Tfelt-Hansen, Peer

AU - Tfelt-Hansen, Jacob

AU - for ESCAPE‐NET

PY - 2019/8

Y1 - 2019/8

N2 - 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.

AB - 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.

U2 - 10.1002/prp2.496

DO - 10.1002/prp2.496

M3 - Journal article

C2 - 31338197

SN - 2052-1707

VL - 7

SP - 1

EP - 9

JO - Pharmacology Research & Perspectives

JF - Pharmacology Research & Perspectives

IS - 4

M1 - e00496

ER -