Updates on Pharmacokinetic Profile of β‐blockers
Introduction
Beta-blockers (β-blockers) are associated with intra-class variability including differences in their pharmacokinetic profile. Determination of intra-class pharmacokinetic as well as pharmacodynamic variability of β-blockers is important with special consideration to aspects relevant to their therapeutics.
A study evaluated the pharmacokinetic variability of β-blockers from 192 publications investigating the pharmacokinetics of oral β-blockers [a coefficient of variance (CV) <40% is considered low or moderate variability, and a CV >40% is considered high variability] among healthy individuals and hypertensive patients.
Results
Figure: Cloud plot of distribution coefficient of variance(CV) in β‐adrenergic blocking agents for the area under plasma-concentration time curve (AUC) in steady‐state studies (SS) and in single‐dose (SD) studies with AUC extrapolated to infinity.
- Metoprolol displayed the highest pharmacokinetic variability followed by propranolol, carvedilol, and nebivolol, based on area under the curve (AUC).
- Bisoprolol demonstrated lowest pharmacokinetic variability followed by atenolol, sotalol, labetalol,
nadolol, and pindolol (Figure).
Pharmacokinetic profile of Bisoprolol includes:
- It is approximately 90% absorbed.
- It has a bioavailability of ~88%.
- It has low lipid solubility.
- It does not undergo major first-pass metabolism.
Conclusion
- Significant pharmacokinetic variability exists amongst patients with respect to different β-blockers. Differences exist in the ratios between highest and lowest steady-state concentrations amongst the β-blockers, with the highest ratio in metoprolol.
- Combination of the known pharmacokinetics of β-blockers with pharmacogenetic findings [cytochrome P450 (CYP)-status for lipophilic β-blockers, pharmacodynamics (pulse or blood pressure) and the individual patient’s characteristics can enable a more personalised treatment approach with minimal adverse effects.
“IND/NONCMCGM/0919/0023”
