Unit Converter
Phenobarbital
Synonyms
- Phenobarbital
- Phenobarbitone
- PB
- PhB
- 5-ethyl-5-phenylbarbituric acid
- Luminal (brand)
Units of Measurement
- µmol/L
- mg/L
- mg/dL
- mg/100 mL
- mg%
- µg/mL
Molecular Weight
232.24 g/mol
Key Unit Conversions
Mass ↔ Molar
1 mg/L=4.31 µmol/L1\ \text{mg/L} = 4.31\ \text{µmol/L}1 mg/L=4.31 µmol/L 1 µmol/L=0.232 mg/L1\ \text{µmol/L} = 0.232\ \text{mg/L}1 µmol/L=0.232 mg/L
mg/dL ↔ mg/L
1 mg/dL=10 mg/L1\ \text{mg/dL} = 10\ \text{mg/L}1 mg/dL=10 mg/L
µg/mL
1 µg/mL=1 mg/L1\ \text{µg/mL} = 1\ \text{mg/L}1 µg/mL=1 mg/L
mg%
\text{mg%} = \text{mg/dL}
Description
Phenobarbital is a long-acting barbiturate antiepileptic that enhances GABA-A receptor activity, increasing chloride influx and raising seizure threshold.
Widely used for:
- Generalized tonic–clonic seizures
- Focal seizures
- Febrile seizures (rarely)
- Neonatal seizures (first-line)
- Status epilepticus (alternative)
Its long half-life (2–5 days) makes therapeutic drug monitoring essential.
Phenobarbital is metabolized in the liver and induces CYP450 enzymes, affecting numerous drug interactions.
Physiological Role
None — phenobarbital is a synthetic pharmacologic agent.
Clinical Significance
Therapeutic Uses
Key antiepileptic drug in:
- Pediatrics
- Low-resource settings
- Neonates
Also used for:
- Sedation
- Treatment of neonatal abstinence syndrome
- Management of hyperbilirubinemia (as enzyme inducer)
HIGH Phenobarbital Levels (Toxicity)
Neurological
- Sedation
- Coma
- Slurred speech
- Respiratory depression
- Ataxia
- Nystagmus
Cardiorespiratory
- Hypotension
- Respiratory failure (life-threatening at high levels)
Other
- Rash
- Cognitive impairment
- Hyperactivity in children (paradoxical)
- Megaloblastic anemia (long-term)
Causes of High Levels
- Excess dosing
- Hepatic impairment
- Drug interactions (valproate inhibits metabolism)
- Elderly or frail patients
- Acute illness reducing clearance
LOW Phenobarbital Levels
- Non-adherence
- Under-dosing
- Rapid metabolic clearance
- CYP450 enzyme induction (rifampicin, carbamazepine)
- Pregnancy (increased clearance)
Reference Intervals (Therapeutic Ranges)
Therapeutic Serum Range
- 10 – 40 mg/L
(= 10–40 µg/mL)
(= 43 – 172 µmol/L)
Critical (Toxic) Level
- > 60 mg/L (high risk of coma / respiratory depression)
Neonatal therapeutic range
- 20 – 40 mg/L
(higher due to immature brain receptors)
Diagnostic Uses
1. Therapeutic Drug Monitoring (Primary Use)
Monitor:
- Efficacy → seizure control
- Safety → avoid toxicity
2. Suspected Toxicity
Check if patient has:
- CNS depression
- Ataxia
- Respiratory slowing
3. Drug Interaction Management
Phenobarbital induces CYP450 → reduces levels of:
- Warfarin
- Steroids
- Calcium channel blockers
- Other antiepileptics
Valproate increases phenobarbital levels by reducing clearance.
4. Neonatal Seizures
Phenobarbital is first-line therapy; levels guide dosing.
5. Liver Disease
Adjust dose due to reduced clearance.
Analytical Notes
- Sample: serum (trough preferred, just before next dose)
- Steady-state achieved in: 10–20 days
- LC–MS/MS or immunoassay
- Hemolysis usually not significant
- Increased free fraction in hypoalbuminemia → greater clinical effect even at normal levels
Clinical Pearls
- Phenobarbital has the longest half-life of all antiepileptics (2–5 days).
- In neonates, half-life can exceed 100 hours.
- Toxicity risk rises sharply above 60 mg/L.
- Elderly patients require lower dosing due to slower metabolism.
- Always check co-medications because phenobarbital is a strong enzyme inducer.
- Valproate → increases phenobarbital levels (dangerous combination).
Interesting Fact
Phenobarbital, discovered in 1912, is one of the oldest epilepsy medications still in use, especially effective in neonatal seizures due to the immature GABAergic system of newborns.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Antiepileptic TDM
- ACCP Clinical Pharmacokinetics - Phenobarbital
- Mayo Clinic Laboratories - Phenobarbital
- ARUP Consult - Antiepileptic Drug Monitoring
- NIH / MedlinePlus - Phenobarbital Test