Pentobarbital Half-Life
The elimination half-life of pentobarbital in adults ranges from 15 to 48 hours, with an average of approximately 15 to 50 hours, and appears to be dose dependent. 1, 2, 3
Pharmacokinetic Properties of Pentobarbital
Pentobarbital is classified as a short-acting barbiturate with the following key pharmacokinetic characteristics:
- Volume of distribution: 0.5-1.0 L/kg 1
- Protein binding: 35-70% 1
- Duration of action: 3-4 hours (clinical effect) 1
- Total endogenous clearance: 18-39 mL/min 1
- Hepatic clearance: 18-37 mL/min 1
- Renal clearance: 0.2-2 mL/min 1
Metabolism and Elimination
Pentobarbital is primarily metabolized by the hepatic microsomal enzyme system. Unlike long-acting barbiturates such as phenobarbital (which has a half-life of 80-120 hours), pentobarbital is almost entirely metabolized in the liver with less than 5% excreted unchanged in the urine 1, 2, 3.
The metabolic products are excreted in the urine and, less commonly, in the feces. The inactive metabolites of barbiturates are typically excreted as conjugates of glucuronic acid 2, 3.
Factors Affecting Half-Life
Several factors can influence pentobarbital's half-life:
- Dose dependence: Higher doses may lead to longer half-lives 2, 3
- Individual variability: Significant inter-patient variability has been observed 4, 5
- Duration of therapy: With prolonged administration, clearance may increase due to autoinduction of hepatic enzymes 5
- Age: Neonates and infants typically have longer half-lives compared to adults 1
Clinical Implications
The relatively long half-life of pentobarbital compared to its duration of action (3-4 hours) is clinically significant:
- In overdose situations, patients may require prolonged supportive care even after clinical improvement 6
- For procedural sedation, while most patients are alert within 30-60 minutes after administration, the duration of sedation can extend up to 106 minutes 1
- When used for brain death determination, assessment should be deferred until adequate elimination of pentobarbital has occurred 1
- In critical care settings with continuous infusions, clearance values show marked variability, necessitating frequent monitoring of plasma levels 5
Special Populations
In patients with severe head injury receiving high-dose continuous intravenous infusions, the mean terminal half-life has been reported as 19.1 hours, with considerable individual variation 4.
For comparison, phenobarbital (a long-acting barbiturate) has a significantly longer half-life of 80-120 hours in adults, 103 hours in term infants, and 141 hours in preterm infants 1, 7.