What is the half-life of metoprolol (beta-blocker) in an adult patient with hypertension?

Half-Life of Metoprolol

The elimination half-life of metoprolol is 3-4 hours in patients with normal CYP2D6 metabolism (extensive metabolizers), but extends to 7-9 hours in poor CYP2D6 metabolizers, who represent approximately 8% of Caucasians and 2% of most other populations. 1

Pharmacokinetic Parameters by Population

Normal Metabolizers (Extensive CYP2D6 Activity)

• Half-life: 3-4 hours after standard oral or intravenous dosing 1
• This represents the majority of patients and forms the basis for standard twice-daily dosing of immediate-release metoprolol tartrate 1
• Clinical studies in healthy volunteers and hypertensive patients confirm this 3-4 hour range 2, 3

Poor CYP2D6 Metabolizers

• Half-life: 7-9 hours, representing a 2-3 fold prolongation compared to extensive metabolizers 1
• These patients exhibit several-fold higher plasma concentrations of metoprolol, which decreases the drug's cardioselectivity 1
• Poor metabolizers may excrete 30-40% of the dose unchanged in urine, compared to less than 10% in extensive metabolizers 1

Special Populations with Altered Half-Life

Hepatic Impairment:

• Half-life is considerably prolonged depending on cirrhosis severity, up to 7.2 hours 1, 4
• The bioavailability increases to 84% (compared to 50% in healthy subjects) due to reduced first-pass metabolism 4
• Total body clearance decreases from 0.80 L/min in controls to 0.61 L/min in cirrhotic patients 4

Geriatric Patients:

• Half-life averages approximately 3.5 hours, similar to younger populations 2
• Despite slightly higher plasma concentrations due to decreased hepatic blood flow and metabolism, the increase is not clinically significant 1
• The FDA label states this difference is "not clinically significant or therapeutically relevant" 1

Renal Impairment:

• No clinically significant change in half-life occurs with chronic renal failure 1
• Dose reduction is usually not needed in patients with renal impairment 1

Clinical Implications of Half-Life

Dosing Frequency

• The 3-4 hour half-life necessitates twice-daily dosing for immediate-release metoprolol tartrate to maintain therapeutic beta-blockade 1
• Extended-release metoprolol succinate formulations allow once-daily dosing despite the short half-life 5
• Some evidence suggests once-daily administration may be possible for hypertension treatment with immediate-release formulations, though twice-daily remains standard 6

Steady-State Considerations

• During extracorporeal treatment for poisoning, the half-life during hemodialysis is 2.9 hours (with metabolite half-life of 5 hours) 7
• During hemoperfusion, the half-life shortens to 2.2 hours 7
• These values demonstrate that extracorporeal removal can modestly enhance clearance, though metoprolol's high volume of distribution (800-1200 L) limits the impact 7

Nonlinear Kinetics Warning

• Evidence of nonlinear kinetics emerges with chronic dosing, where steady-state area under the curve can be 86.8% higher than predicted from single-dose kinetics 3
• This occurs because pre-systemic metabolism is saturable, leading to non-proportionate increases in exposure with increased doses 1
• Single-dose kinetic data are poor predictors of steady-state kinetics 3

Common Pitfalls

• Do not assume the 3-4 hour half-life means metoprolol requires dosing every 3-4 hours; the duration of pharmacodynamic effect (beta-blockade) exceeds the elimination half-life, supporting twice-daily dosing 6, 8
• Do not overlook CYP2D6 polymorphism when patients exhibit excessive bradycardia or hypotension at standard doses—they may be poor metabolizers with 2-3 fold higher drug exposure 1
• Do not reduce doses in renal failure based on half-life concerns; renal impairment does not significantly alter metoprolol elimination 1
• Do adjust doses and monitor carefully in hepatic impairment, where half-life can double and bioavailability increases substantially 1, 4