From the Guidelines
The elimination half-life of metoprolol is approximately 3-7 hours, as indicated in the 2024 guideline for the diagnosis and management of atrial fibrillation 1. This means that after this time period, half of the drug has been eliminated from the body.
- Complete clearance of metoprolol from the system typically takes about 5 half-lives, so approximately 15-35 hours.
- The variation in half-life occurs because metoprolol is metabolized primarily by the liver enzyme CYP2D6, which has genetic variations in the population affecting metabolism speed.
- Patients with reduced CYP2D6 activity (poor metabolizers) may experience longer half-lives and potentially stronger effects from standard doses. The relatively short half-life explains why immediate-release metoprolol is typically dosed twice daily, while extended-release formulations can be taken once daily for effective blood pressure and heart rate control, as outlined in the guideline 1.
- The guideline provides specific dosing recommendations for metoprolol, including an oral maintenance dose of 25–200 mg, twice daily, and an elimination half-life of 3–4 hours for metoprolol tartrate, and 3–7 hours for metoprolol succinate 1. It is essential to consider the specific formulation and individual patient factors when determining the optimal dosing schedule for metoprolol, as supported by the evidence from the 2024 guideline 1.
From the FDA Drug Label
Elimination of metoprolol is mainly by biotransformation in the liver The mean elimination half-life of metoprolol is 3 to 4 hours; in poor CYP2D6 metabolizers the half-life may be 7 to 9 hours. The elimination half-life of metoprolol is 3 to 4 hours in most subjects, but it may be 7 to 9 hours in poor CYP2D6 metabolizers 2.
- Key points:
- Mean elimination half-life: 3 to 4 hours
- Elimination half-life in poor CYP2D6 metabolizers: 7 to 9 hours
From the Research
Metoprolol Elimination Half-Life
- The elimination half-life of metoprolol is not explicitly stated in the provided studies 3, 4, 5, 6, 7.
- However, the study by 4 provides information on the pharmacokinetics of metoprolol, including its plasma concentration-time profiles and pharmacokinetic parameters such as clearance and area under the concentration-time curve.
- The study by 4 mentions that metoprolol has a dose-dependent increase in maximum plasma concentration, time to reach maximum plasma concentration, and area under the concentration-time curve, but does not provide a specific value for the elimination half-life.
- Another study by 3 discusses the pharmacodynamic and pharmacokinetic properties of metoprolol, but also does not provide a specific value for the elimination half-life.
Factors Affecting Metoprolol Elimination
- The study by 4 suggests that the pharmacokinetics of metoprolol can be affected by various factors, including renal impairment, hepatic cirrhosis, and co-administration with other drugs.
- For example, patients with renal impairment showed an increase in clearance of metoprolol, while patients with hepatic cirrhosis showed a decrease in clearance.
- The study by 4 also mentions that metoprolol can interact with other drugs, which can affect its pharmacokinetics and potentially lead to adverse effects.
Clinical Implications
- The study by 7 highlights the importance of considering the beta blocker rebound phenomenon when discontinuing metoprolol or other beta blockers.
- The study suggests that the discontinuation of beta blockers can lead to dangerous consequences, including an increased risk of coronary artery disease, angina pectoris, and mortality.
- However, the study also notes that there is a lack of information on the definition, incidence, and optimal prevention strategies for the beta blocker rebound phenomenon.