What is the half-life of metoprolol (beta-blocker) succinate?

Half-Life of Metoprolol Succinate

The elimination half-life of metoprolol succinate is 3 to 4 hours in most individuals, but may be prolonged to 7 to 9 hours in poor CYP2D6 metabolizers. 1

Pharmacokinetic Properties

• Metoprolol is primarily metabolized by CYP2D6 in the liver, with approximately 95% of the dose recoverable in urine 1
• In normal metabolizers (extensive metabolizers), less than 10% of an intravenous dose is excreted as unchanged drug in urine 1
• In poor metabolizers (approximately 8% of Caucasians and 2% of other populations), up to 30-40% of oral or intravenous doses may be excreted unchanged 1
• The volume of distribution for metoprolol ranges from 3.2 to 5.6 L/kg 1
• About 10% of metoprolol in plasma is bound to serum albumin 1

Formulation Differences

• Metoprolol succinate (extended-release) is designed to deliver the drug at a near constant rate for approximately 20 hours 2, 3
• The extended-release formulation produces even plasma concentrations over a 24-hour period without the marked peaks and troughs seen with immediate-release metoprolol tartrate 2
• A 100-mg metoprolol controlled/extended-release tablet contains 95 mg of metoprolol succinate and is considered to have equivalent activity to 100 mg metoprolol tartrate 4
• After ingestion, the extended-release tablet disintegrates into individual pellets, with each pellet acting as a diffusion cell releasing the drug at a relatively constant rate 4

Special Populations

• Geriatric patients: May show slightly higher plasma concentrations due to decreased metabolism and hepatic blood flow, but this increase is not clinically significant 1
• Renal impairment: The systemic availability and half-life do not differ significantly from normal subjects, so no dosage adjustment is usually needed 1
• Hepatic impairment: The elimination half-life can be considerably prolonged, up to 7.2 hours, depending on severity of impairment 1

Clinical Implications

• The extended-release formulation allows for once-daily dosing due to its pharmacokinetic profile, despite the relatively short half-life of the active compound 2, 3
• Metoprolol's cardioselectivity is well maintained with the extended-release formulation at doses up to 200 mg daily 3
• The consistent beta-1 blockade over 24 hours with the extended-release formulation has been demonstrated to improve outcomes in heart failure patients 5
• When switching from intravenous to oral therapy, the first oral dose should be given 15 minutes after the last intravenous dose to maintain therapeutic effect 6

Monitoring Considerations

• Due to the half-life and onset of action (1-2 hours), monitoring of heart rate and blood pressure is recommended during initiation and dose titration 6
• Target parameters typically include a resting heart rate of 50-60 beats per minute unless limiting side effects are reached 6
• Patients should be monitored for signs of bradycardia, hypotension, and bronchospasm during the onset period 6

The pharmacokinetic profile of metoprolol succinate, despite its 3-4 hour half-life, supports once-daily dosing through its controlled-release formulation, providing consistent beta-blockade over 24 hours while maintaining cardioselectivity.