Half-Life of Intravenous Metoprolol
The elimination half-life of intravenous metoprolol is 3 to 4 hours in most patients (extensive CYP2D6 metabolizers), but may be prolonged to 7 to 9 hours in poor CYP2D6 metabolizers. 1
Pharmacokinetic Details
The FDA-approved drug label provides the definitive pharmacokinetic parameters for IV metoprolol:
Standard elimination half-life: 3-4 hours in patients with normal CYP2D6 metabolism (extensive metabolizers), who represent approximately 92% of Caucasians and 98% of most other populations 1
Prolonged half-life: 7-9 hours in poor CYP2D6 metabolizers, who comprise about 8% of Caucasians and 2% of most other populations 1
Distribution half-life: 5-30 minutes, indicating rapid tissue distribution after IV administration 2
Clinical Implications of Half-Life
The relatively short half-life of IV metoprolol has important clinical consequences:
Maximum beta-blockade is achieved at approximately 20 minutes after IV infusion over a 10-minute period 1
Less than 10% of an IV dose is excreted unchanged in urine in extensive metabolizers, while up to 40% may be excreted unchanged in poor metabolizers 1
The short half-life necessitates transition to oral therapy within 15 minutes after the last IV dose to maintain therapeutic effect, typically starting with 25-50 mg orally every 6 hours 3
Factors Affecting Half-Life
Several patient-specific factors can alter metoprolol's elimination half-life:
Hepatic impairment significantly prolongs half-life up to 7.2 hours depending on severity, since the drug is primarily eliminated by hepatic metabolism 1
Renal impairment does not clinically affect half-life in a significant way, as systemic availability and half-life in patients with renal failure do not differ meaningfully from normal subjects 1
Geriatric patients may show slightly higher plasma concentrations due to decreased hepatic metabolism and blood flow, though this is not clinically significant for half-life 1
Comparison with Other Beta-Blockers
Research data from extracorporeal treatment studies provides comparative context:
Metoprolol's half-life during hemodialysis was 2.9 hours (with metabolite half-life of 5 hours), consistent with the FDA label 4
This is shorter than atenolol (HD half-life 4.6 hours) but longer than esmolol (HD half-life 0.12 hours) 4
Historical pharmacokinetic studies from the 1970s-1980s confirmed the 3-4 hour elimination half-life range in various patient populations 5, 2, 6