Half-Life of Midazolam (Versed)
The half-life of midazolam (Versed) is approximately 1.8 to 6.4 hours in healthy adults, with a mean of approximately 3 hours. 1
Pharmacokinetic Properties
Midazolam is a water-soluble, short-acting benzodiazepine with unique pharmacokinetic properties:
- Onset of action: 1-2 minutes after IV administration 2
- Peak effect: Achieved within 3-4 minutes 2
- Duration of effect: 15-80 minutes 3
- Volume of distribution: 1.0 to 3.1 L/kg 1
- Total clearance: 0.25 to 0.54 L/hr/kg 1
Factors Affecting Half-Life
Several patient factors can significantly alter midazolam's half-life:
- Age: Elderly patients (mean age 73) have approximately two-fold higher plasma half-life compared to younger patients 1
- Obesity: Obese patients have a longer half-life (5.9 hours vs 2.3 hours in normal-weight individuals) due to approximately 50% increase in volume of distribution 1
- Hepatic impairment: Patients with alcoholic cirrhosis have a 2.5-fold increase in half-life and 50% reduction in clearance 1
- Renal impairment: Patients with acute renal failure have prolonged half-life (13 hours vs 7.6 hours) 1
- Congestive heart failure: Approximately two-fold increase in elimination half-life 1
Clinical Implications
The relatively short half-life of midazolam compared to other benzodiazepines has important clinical implications:
- Midazolam is distinguished from other benzodiazepines by its more rapid onset and shorter duration of effect 3
- Despite its short half-life, respiratory depression can persist, with apnea potentially occurring up to 30 minutes after the last dose 2
- Re-sedation may occur because the effects of midazolam may persist for 80 minutes or longer 3
- Flumazenil (benzodiazepine antagonist) has a half-life of 0.7-1.3 hours, which is shorter than midazolam, creating potential for re-sedation after reversal 3
Special Populations
- Pediatric patients: Terminal elimination half-life (0.78 to 3.3 hours) is similar to or shorter than in adults, except in seriously ill neonates where it is substantially prolonged (6.5 to 12.0 hours) 1
- Drug interactions: Medications that inhibit cytochrome P450-3A4 can inhibit midazolam clearance and elevate steady-state concentrations, potentially prolonging half-life 1
The short elimination half-life and absence of clinically important long-acting metabolites make midazolam suitable for procedural sedation and short-term use 4, but careful monitoring is essential, especially in high-risk populations with factors that may prolong its half-life.