What is the half-life of propofol (intravenous anesthetic agent)?

Propofol Half-Life

Propofol has a rapid onset of action (30-45 seconds) with a short initial distribution half-life of 2-8 minutes, followed by a terminal elimination half-life of 4-7 hours. 1

Pharmacokinetic Profile

Propofol demonstrates a complex pharmacokinetic profile characterized by three distinct phases:

1. Initial Distribution Phase:

   • Half-life: 2-8 minutes
   • Represents rapid equilibration between plasma and highly perfused tissues (including brain)
   • Accounts for rapid onset of action and initial awakening

2. Intermediate Phase:

   • Half-life: 30-60 minutes
   • Reflects redistribution from brain to muscle and other tissues

3. Terminal Elimination Phase:

   • Half-life: 4-7 hours (can extend to 1-3 days after prolonged infusion) 2
   • Represents slow elimination from poorly perfused tissues

Clinical Implications

The multi-compartment pharmacokinetics of propofol explain its clinical utility:

• Rapid onset: Due to high lipophilicity and rapid blood-brain barrier penetration
• Short duration after single dose: Due to redistribution rather than elimination
• Context-sensitive half-time: Increases with infusion duration

Factors Affecting Propofol Pharmacokinetics

• Age: Elderly patients have decreased clearance and smaller central volume of distribution, requiring lower doses 2
• Organ dysfunction: Hepatic and renal impairment do not significantly alter pharmacokinetics 1
• Infusion duration: Prolonged infusions lead to tissue accumulation, extending recovery time 2

Clinical Considerations

When using propofol for sedation or anesthesia:

• Short procedures: Rapid recovery can be expected after single doses or short infusions
• Prolonged infusions: Consider that:
  • Tissue saturation occurs, slowing redistribution
  • Recovery time increases with infusion duration
  • Reducing infusion rates by up to 50% may be appropriate for long-term administration 2

Important Caveats

1. Propofol Infusion Syndrome (PRIS):

   • Rare but potentially fatal complication
   • Associated with high-dose (>4 mg/kg/hr) prolonged (>48 hours) infusions
   • Characterized by metabolic acidosis, rhabdomyolysis, arrhythmias, and organ failure 3

2. Cardiorespiratory Effects:

   • Dose-dependent respiratory depression
   • Hypotension due to vasodilation
   • More pronounced in hemodynamically unstable patients 1

3. Formulation Considerations:

   • Contains egg lecithin and soybean oil (potential allergens)
   • Some formulations contain sulfite preservatives 4
   • Supports bacterial growth (strict aseptic technique required)

The rapid onset and short duration of action after single doses or brief infusions make propofol ideal for short procedures requiring rapid recovery, despite its longer terminal elimination half-life.