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

Propranolol Half-Life

The half-life of propranolol is approximately 3-5 hours for the immediate-release formulation, with significant variability between individuals. 1, 2

Pharmacokinetic Profile

Propranolol is a highly lipophilic beta-blocker with the following key pharmacokinetic properties:

• Absorption: Almost completely absorbed after oral administration but undergoes extensive first-pass metabolism in the liver, with only about 25% reaching systemic circulation 2

• Distribution:

  • Approximately 90% bound to plasma proteins (albumin and alpha1-acid glycoprotein) 2
  • Volume of distribution is approximately 4 liters/kg 2
  • Crosses the blood-brain barrier and placenta, and is distributed into breast milk 2

• Metabolism:

  • Extensively metabolized through three primary routes:
    • Aromatic hydroxylation (mainly 4-hydroxylation) - 42%
    • N-dealkylation followed by side-chain oxidation - 41%
    • Direct glucuronidation - 17%
  • Metabolism shows considerable variability between individuals 2
  • Aromatic hydroxylation is catalyzed mainly by polymorphic CYP2D6 2

Factors Affecting Half-Life

The half-life of propranolol can be influenced by several factors:

• Age: Elderly patients (62-79 years) show prolonged half-life compared to younger adults (25-33 years) - approximately 11 hours vs. 5 hours 2

• Formulation:

  • Immediate-release: 3-5 hours 1
  • Extended-release: 8-11 hours due to slower absorption from the gut 3

• Dosing schedule:

  • With chronic administration, the half-life may be prolonged to 3-6 hours as hepatic removal processes become saturated 1

• Individual variability:

  • Up to 20-fold variation in plasma levels can occur after chronic administration of the same oral dose to different patients 1
  • Variations in plasma protein binding affect distribution and half-life 1

Clinical Implications

• For immediate-release propranolol, the short half-life typically necessitates multiple daily dosing to maintain therapeutic effects 3

• When administered intravenously for acute treatment of SVT, propranolol is given as a 1 mg IV dose over 1 minute, which can be repeated at 2-minute intervals up to 3 doses 4

• The extended-release formulation was developed to maintain therapeutic plasma concentrations throughout a 24-hour period while allowing once-daily dosing 3

• Due to propranolol's high endogenous clearance and volume of distribution, it will not be removed meaningfully by extracorporeal treatment modalities in cases of overdose 4

Precautions and Contraindications

Propranolol should be used with caution or avoided in patients with:

• AV block greater than first degree or SA node dysfunction (in absence of pacemaker)
• Decompensated heart failure
• Cardiogenic shock
• Reactive airway disease
• Concomitant use of verapamil or digoxin 4

The drug's effects typically dissipate within 24-48 hours after discontinuation, but abrupt withdrawal should be avoided due to potential rebound effects including angina, arrhythmias, and infarction 1.