Half-life of Ketamine
The half-life of ketamine is approximately 2.5 hours for the redistribution phase (beta phase) following intravenous administration. 1
Pharmacokinetic Profile of Ketamine
Ketamine's pharmacokinetics follow a multi-phase pattern:
- Initial phase (alpha phase): 10-15 minutes half-life, lasting about 45 minutes 1
- This corresponds to the primary anesthetic effect
- Redistribution phase (beta phase): 2.5 hours half-life 1
- Represents redistribution from CNS to peripheral tissues
- Terminal elimination half-life: 5.2-6.1 hours 2
Route of Administration Effects
The pharmacokinetic profile varies based on administration route:
- IV administration: Rapid onset (1 minute) with short duration of effect (15-30 minutes) 3
- Oral administration: Significantly different profile with greater formation of metabolites, particularly 2,6-hydroxynorketamines 2
Metabolism and Elimination
Ketamine undergoes extensive hepatic metabolism:
- Primary metabolism via N-dealkylation to norketamine (active metabolite) 1
- Secondary metabolism to hydroxynorketamine compounds 1
- Further metabolism to dehydroxynorketamine 1
Elimination occurs primarily through the kidneys, with only a small percentage excreted as unchanged ketamine in urine 4.
Clinical Implications of Ketamine's Half-life
The relatively short half-life of ketamine has important clinical implications:
- Short duration of action: The anesthetic effect typically lasts 15-30 minutes following IV administration 3
- Recovery profile: Patients typically recover from anesthesia when plasma concentrations fall to approximately 2.7 μmol/L 5
- Monitoring duration: Despite the short half-life, patients should be monitored for a longer period due to potential emergence reactions 3
Important Considerations
- Active metabolites: Norketamine has approximately 1/3 the activity of ketamine 1
- Cardiovascular effects: Blood pressure and heart rate elevations typically return to baseline within 15 minutes 1
- Emergence reactions: May occur in 10-30% of adults during the recovery phase 3
- Drug interactions: Benzodiazepines can be used to reduce emergence reactions 3
Special Populations
The pharmacokinetics of ketamine may be altered in certain populations:
- Hepatic impairment: May result in prolonged elimination 1
- Elderly: Require dose reduction due to altered pharmacokinetics 6
The multi-phase elimination profile of ketamine explains why its clinical effects are relatively short-lived despite a longer terminal half-life, as the redistribution from CNS to peripheral tissues is the primary determinant of the duration of clinical effect.