Unit Converter
Valproic Acid
(Antiepileptic Drug - Requires Therapeutic Drug Monitoring for Safety & Efficacy)
Synonyms
- VPA
- Valproate
- Sodium valproate
- Divalproex sodium
- 2-propylpentanoic acid
- Depakote® / Epival® (brand names)
Units of Measurement
- µmol/L
- mg/L
- mg/dL
- mg/100 mL
- mg%
- µg/mL
Unit Conversions
Molecular Weight of Valproic Acid = 144.21 g/mol
µmol/L → mg/L
1 µmol/L=0.144 mg/L1\ \text{µmol/L} = 0.144\ \text{mg/L}1 µmol/L=0.144 mg/L 1 mg/L=6.93 µmol/L1\ \text{mg/L} = 6.93\ \text{µmol/L}1 mg/L=6.93 µmol/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 → mg/L
1 µg/mL=1 mg/L1\ \text{µg/mL} = 1\ \text{mg/L}1 µg/mL=1 mg/L
mg/100 mL = mg% = mg/dL
Description
Valproic acid is a broad-spectrum antiepileptic drug (AED) used to treat:
- Generalized seizures
- Focal seizures
- Absence seizures
- Bipolar disorder (mania)
- Migraine prophylaxis
It works by:
- Increasing GABA concentration
- Inhibiting voltage-gated sodium channels
- Reducing excitatory neurotransmission
It has a narrow therapeutic index, and serum monitoring is essential to balance efficacy with toxicity.
Pharmacology & Mechanism
- Highly protein-bound (~90% to albumin)
- Free fraction increases in:
- Hypoalbuminemia
- Pregnancy
- Renal failure
- Critical illness
- Hypoalbuminemia
- Metabolized by liver (UGT + β-oxidation + CYP enzymes)
- Non-linear kinetics at high levels
- Half-life ~8–20 hours
Clinical Significance
HIGH VALPROIC ACID LEVELS
Major Toxic Effects
- CNS depression
- Ataxia
- Tremors
- Confusion, lethargy, coma
- Hyperammonemia → encephalopathy
- Hepatotoxicity (especially in children <2 years)
- Pancreatitis
- Thrombocytopenia / bone marrow suppression
- Metabolic acidosis
- Alopecia (chronic)
Risk Factors for Toxicity
- Hypoalbuminemia (↑ free drug)
- Drug interactions (aspirin, phenytoin)
- Overdose
- Liver disease
LOW VALPROIC ACID LEVELS
→ Subtherapeutic, risk of seizures or relapse of mania.
Causes:
- Non-adherence
- Poor absorption
- Drug interactions (carbamazepine, topiramate)
- Hypermetabolic states
- Pregnancy (↑ clearance)
Reference Intervals
(ACCP, Mayo, ARUP, Tietz 8E)
Total Valproic Acid
- 50 – 100 µg/mL
(= 50–100 mg/L)
(= 347–694 µmol/L)
Extended Range for Mania / Some Epilepsies
- 50 – 125 µg/mL
Toxic Level
- >150 µg/mL (risk of CNS & hepatic toxicity)
- >200 µg/mL (severe toxicity, ICU care)
Free (Unbound) Valproic Acid
Particularly important in:
- Pregnancy
- Renal failure
- Hypoalbuminemia
- ICU patients
Therapeutic Free VPA
- 6 – 22 µg/mL
Diagnostic Uses
1. Seizure Disorder Management
Maintain therapeutic levels to prevent breakthrough seizures.
2. Bipolar Disorder (Acute Mania)
Dose titration guided by serum VPA levels.
3. Migraine Prophylaxis
Therapeutic levels ensure adequate prevention.
4. Overdose Assessment
Early and serial levels guide decontamination and supportive care.
5. Free VPA Monitoring
When total VPA is misleading due to low albumin.
6. Hyperammonemia Evaluation
VPA may cause carnitine depletion → ↑ ammonia → encephalopathy.
Analytical Notes
- Sample: serum or plasma
- Timing: trough level (just before next dose)
- Hemolysis minimal effect
- Valproate interferes with some assays for:
- Bilirubin
- TSH
- Bilirubin
- LC-MS/MS gives the most accurate results
Clinical Pearls
- Free VPA is what correlates with toxicity - especially in hypoalbuminemia.
- Ammonia levels should be checked if patient on VPA becomes confused.
- VPA is highly teratogenic - avoid in pregnancy; monitor levels closely.
- Carbapenems (meropenem) drastically reduce VPA → seizure breakthrough.
- Chronic VPA therapy may cause carnitine deficiency → supplement if symptomatic.
Interesting Fact
Valproic acid was originally used in the 1960s as a solvent for other drugs-its anticonvulsant properties were discovered accidentally during laboratory testing.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Therapeutic Drug Monitoring
- ACCP Guidelines - Antiepileptic Drug TDM
- ILAE Antiseizure Medication Guidance
- Mayo Clinic Laboratories - Valproic Acid
- ARUP Consult - Anticonvulsant Drug Monitoring
- NIH / MedlinePlus - VPA Monitorin