Valproic Acid (Total)
The total amount of valproic acid (valproate), a seizure and mood medicine, in your blood, usually checked just before your next dose.
AI-verified against cited sources. Awaiting expert reviewAlso called VPALOINC 4086-5
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What it is
Valproic acid, also called valproate (brand names include Depakote and Depakene), is used to treat seizures and bipolar disorder and to help prevent migraines. This test measures the total amount in your blood: the large part attached to blood proteins and the smaller free part. Blood is usually drawn right before your next dose, when the level is lowest (the trough).
Why it matters
Doctors check the level to see whether the dose is in the range where most people get benefit with fewer side effects, to confirm the medicine is being taken as prescribed, and when another medicine or illness might change the level. Most valproate is attached to the protein albumin. When albumin is low, or when other medicines compete for the same spots, the free part can be high even if the total looks fine.
If it’s low
A low level means less valproate in the blood than the usual range. That can mean less protection against seizures or mood symptoms, although some people do well at lower levels. The most common reason is a missed or late dose.
Common causes
- Missed or late doses
- Blood drawn long after the last dose
- Carbapenem antibiotics, which can lower valproate levels quickly
- Medicines that speed up valproate clearance, such as phenytoin or carbamazepine
- Some other medicines, such as methotrexate
What can help
- Tell your clinician about any missed doses and any new antibiotics or other medicines
- Ask whether the level should be repeated before the dose is changed
- Talk with your clinician before making any change to your dose
If it’s high
A high level means more valproate in the blood than the usual range. Higher levels are linked to more side effects, such as sleepiness, shaking, nausea, low platelet counts and sometimes a raised ammonia level. Many people feel well at levels a little above the range, so your clinician will weigh the number with how you feel and your other labs.
Common causes
- A recent dose increase
- Blood drawn soon after a dose instead of right before it
- Slower clearance, for example with liver disease or older age
- Medicines that slow valproate breakdown, such as felbamate
- Taking more than prescribed
What can help
- Ask your clinician whether a free valproate level, a platelet count or an ammonia level would help interpret the result
- Tell your clinician about every medicine and supplement you take, including aspirin
- Talk with your clinician before making any change to your dose
Usual ranges
What labs print as the reference range, by who was tested. Ranges differ a little between labs, so the range on your own report is the one your result is judged against.
For adults: 50–100 µg/mL. Source: Quest Diagnostics, DailyMed, National Library of Medicine, Drug Design, Development and Therapy, ARUP Laboratories. Labs treat above 150 µg/mL as urgent.
- Adults (this one applies)50–100 µg/mL
Sources: Quest Diagnostics, DailyMed, National Library of Medicine, Drug Design, Development and Therapy, ARUP Laboratories
What can affect your result
- Time since your last dose, and whether the sample is a true trough
- Albumin level and kidney function, which change how much of the drug is free
- Other medicines: carbapenem antibiotics and enzyme inducers lower levels, while felbamate raises them and aspirin raises the free fraction
- Age: older adults clear the unbound drug more slowly
- Pregnancy, when free valproate can matter more
- Dosage form (immediate-release or extended-release)
- A sample drawn soon after a dose reads higher than a trough.
- Protein binding is saturable: when albumin is low, in kidney disease, or with drugs that compete for binding (aspirin, for example), the free level can be high while the total looks normal.
- Carbapenem antibiotics (such as meropenem, imipenem or ertapenem) can lower valproate levels sharply within days.
- Quest rejects serum separator (gel) tubes for this test; it asks for a red-top tube without gel (plasma in EDTA or heparin tubes is also accepted).
Right before the next dose (a trough) at steady state, which usually means after about a week of the same dose. A change in dose usually takes several days to settle into a new steady-state level. Carbapenem antibiotics can lower levels quickly.
When to talk to a clinician
Contact your clinician promptly for unusual sleepiness, confusion, repeated vomiting, easy bruising or bleeding, yellowing of the skin or eyes, or severe belly pain. Many hospitals ask the care team to call about levels above 150 µg/mL. Call 911 or your local emergency number for very deep drowsiness, trouble breathing, a seizure that does not stop, or fainting.
Questions you could ask
- What level are we aiming for in my case?
- Do my albumin or kidney results change how this should be read?
- How often should this be checked, and should my platelets be checked too?
- Was my blood drawn right before a dose?
- Would a free valproate level, a platelet count or an ammonia level help?
- Could another medicine or supplement be raising my level?
Questions people ask
Why does one lab print 50–100 and another 50–125?
Both ranges are in use. FDA labeling gives 50–100 mcg/mL as the usually accepted range for seizures, and Quest prints 50.0–100.0 mg/L. In studies of acute mania, people were dosed to trough levels of 50–125 mcg/mL, and ARUP prints 50–125 µg/mL. Your clinician chooses the target that fits your condition.
What is a free valproate level, and why might I need one?
Most valproate in the blood is attached to protein, and only the free part is thought to act in the body. The total level can look normal while the free part is high when albumin is low, in kidney disease, in pregnancy, or when other medicines compete for the protein. ARUP lists a free range of 7–23 µg/mL. Ask your clinician whether a free level would help.
How do I convert µg/mL to µmol/L?
Multiply µg/mL (the same as mg/L) by 6.93. So 50 µg/mL is about 347 µmol/L and 100 µg/mL is about 693 µmol/L. To go the other way, multiply µmol/L by 0.1442.
Show the science and sources
Units
- 1 µg/mL = 1 µg/mL
- 1 µg/mL = 1 mg/L
- 1 µg/mL = 6.934 µmol/L
Open the Valproic acid unit converter
For clinicians and researchers
Valproate is highly protein bound with concentration-dependent (saturable) binding, so the free fraction rises with total concentration and in hypoalbuminemia, renal failure and with displacing drugs; free fraction is usually under about 10% at common concentrations (Reimers 2018). ARUP lists total 50–125 µg/mL (toxic above 150), free 7–23 µg/mL (toxic above 30) and percent free 5–18%, and prefers the free and total panel in renal failure or conditions that alter albumin. FDA labeling gives 50–100 mcg/mL as the usually accepted range, acute-mania trials dosed to troughs of 50–125 mcg/mL, and states that the probability of thrombocytopenia rises significantly at total trough concentrations above 110 mcg/mL in females and above 135 mcg/mL in males. Textbooks give a lower limit of 50 mg/L and an upper limit of 100 or 125 mg/L, and a 2018 review for Norwegian guidelines recommended 300–700 µmol/L (43–101 mg/L). Carbapenems can reduce serum valproate to subtherapeutic levels, and enzyme inducers, felbamate, aspirin and methotrexate also change levels. Hyperammonemia can occur with normal liver tests (FDA labeling). Patients have recovered from reported levels as high as 2,120 mcg/mL (FDA labeling). Hospital critical limits vary (median 150, range 100–400 µg/mL).
LOINC 4086-5 (primary), 4088-1, 14946-8. Specimen: serum-or-plasma.
Sources
- Valproic Acid (test code 916), Quest Diagnostics
- Valproic Acid, Free and Total (test 0099310), ARUP Laboratories
- Depakote (divalproex sodium) prescribing information, DailyMed, National Library of Medicine
- Reference ranges for antiepileptic drugs revisited: a practical approach to establish national guidelines, Drug Design, Development and Therapy (2018)
- Drug Critical Limits for Urgent Physician Notification, Clinical Pharmacology & Therapeutics (Kuang, Ibrahim, Cheng, Kost) (2026)
- Valproic acid (PubChem compound 3121), PubChem, National Library of Medicine
AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.