What is the half-life of neostigmine?

Half-life of Neostigmine

Neostigmine has a half-life of 15-30 minutes when administered intravenously. 1

Pharmacokinetic Properties

• Neostigmine is a quaternary ammonium compound that functions as a reversible acetylcholinesterase inhibitor 2
• The elimination half-life of neostigmine ranges from 15 to 30 minutes following intravenous administration 1, 3
• More specifically, studies have shown the elimination half-life varies between:
  • 15.4 to 31.7 minutes in anesthesia patients 3
  • 24 to 113 minutes in some pharmacokinetic studies 4
  • 51.1 to 90.5 minutes after intramuscular administration in myasthenia gravis patients 5

Clinical Implications in Anesthesia

• Neostigmine's relatively short half-life makes it suitable for reversing non-depolarizing neuromuscular blockade in anesthesia 2
• The drug increases acetylcholine concentration in the synaptic cleft, competing with non-depolarizing muscle relaxants at the neuromuscular junction 2, 4
• Maximum pharmacological effect typically occurs between 7-15 minutes after intravenous administration 3

Pharmacokinetic Considerations

• Neostigmine has a plasma clearance of 0.5-1.0 L/h/kg 6
• The observed volume of distribution ranges from 0.12 to 1.4 L/kg following intravenous injection 4
• The drug is metabolized by microsomal enzymes in the liver 4
• Approximately 80% is eliminated in urine within 24 hours, with about 50% as unchanged drug 5

Special Populations

• In pediatric patients:
  • Elimination half-life is 39 ± 5 minutes in infants (2-10 months)
  • Elimination half-life is 48 ± 16 minutes in children (1-6 years) 4
• In patients with renal impairment:
  • Half-life is prolonged in patients with impaired renal function
  • Elimination half-life for normal, transplant, and anephric patients were 79.8 ± 48.6,104.7 ± 64, and 181 ± 54 minutes, respectively 4

Clinical Dosing Implications

• The standard dose of neostigmine for reversal of neuromuscular blockade is 40-50 mcg/kg of ideal body weight 2
• Due to its relatively short half-life, neostigmine should only be administered when there are at least 4 responses to train-of-four stimulation 2, 7
• Quantitative monitoring should continue after administration until a TOF ratio ≥0.9 is achieved 2

Important Caveats

• Neostigmine should not be administered when TOF ratio is already >0.9, as it may paradoxically impair neuromuscular transmission 2
• An anticholinergic agent (atropine or glycopyrrolate) should be administered with neostigmine to prevent cholinergic side effects due to its short half-life and rapid onset of action 2
• For very slight residual blockade, consider reducing the neostigmine dose to 20 mcg/kg to avoid potential adverse effects 2