Valproic Acid Level 

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Valproic acid is an 8-carbon 2-chain fatty acid that is metabolized by the liver and processed at a variable rate based on the patient’s liver function and age, in addition to patient’s other routine medications with which valproic acid may interact. At therapeutic concentrations, valproic acid mediates prolonged recovery of voltage-activated Na+ channels, thereby inhibiting repetitive firing induced by depolarization of cortical and spinal cord neurons. Its action is similar to that of other common anticonvulsants, such as phenytoin and carbamazepine.

The reference ranges for valproic acid are as follows: ^{[1, 2, 3]}

The therapeutic range for valproic acid (total) is 50-125 µg/mL. The toxic level is greater than 150 µg/mL.

The therapeutic range for valproic acid (free) is 6-22 µg/mL. The toxic level is greater than 50 µg/mL; above this threshold concentration, the binding sites on plasma albumin begin to become saturated.

The recommended range for the treatment of epilepsy is 50-100 µg/mL total valproic acid. The recommended range for the treatment of acute mania is 85-125 µg/mL total valproic acid.

Valproic acid is a broad-spectrum antiseizure drug with a narrow therapeutic window. It is absorbed rapidly and completely after oral administration, with peak plasma concentrations observed in 1-4 hours. Within the therapeutic ranges listed above, most patients experience therapeutic drug effects without excessive side effects. Even within the recommended therapeutic range, however, results vary between individual patients and some may experience adverse effects at the low end of the spectrum. The range of effectiveness and adverse reactions seen with this drug require monitoring of serial drug levels to ensure optimized dosing for each individual patient. ^{[4, 3]}

Generally, the dosage is considered optimal if the valproic acid level is within the therapeutic range and the patient is receiving treatment benefits (eg, suppression of seizures or mood swings) without adverse effects. Valproic acid levels should be obtained on patients taking this medication regularly for medical treatment and should also be considered in addition to standard toxicology panels when ingestion or overdose of valproic acid is suspected.

See the list below:

Specimen type: Whole blood; draw volume is 0.6 mL ^[4]

Container: Green-top (lithium Heparin) tube; an alternative is the red-top (plain, no gel) tube

Panels: Valproic acid levels are not traditionally included in standard toxicology panels; however, they should be considered on a case-specific basis when evaluating patients with known seizure disorder, patients presenting with altered mental status, and in patients suspected of drug ingestion/overdose

Valproic acid is an 8-carbon 2-chain fatty acid that is metabolized by the liver and processed at a variable rate based on the patient’s liver function and age, in addition to patient’s other routine medications with which valproic acid may interact. At therapeutic concentrations, valproic acid mediates prolonged recovery of voltage-activated Na+ channels, thereby inhibiting repetitive firing induced by depolarization of cortical and spinal cord neurons. Its action is similar to that of other common anticonvulsants, such as phenytoin and carbamazepine. ^[3]

Valproic acid is used for the treatment and control of conditions such as the following: ^{[1, 2, 4, 3, 5]}

Simple and complex partial seizures

Absence seizures

Generalized tonic-clonic seizures

Myoclonic epilepsy

Acute and maintenance therapy of bipolar disease

Migraine prophylaxis

Chronic pain syndromes

A valproic acid level measures the amount of valproic acid in the blood: either the total level or free level of the drug. Monitoring of serial valproic acid levels is required to maintain the drug within the narrow recommended therapeutic range. Subtherapeutic levels place the patient at risk of recurrence of the condition for which they are taking valproic acid, and supratherapeutic levels place the patient at risk of adverse and toxic side effects.

Dosages of valproic acid must be adjusted carefully based on valproic acid blood levels until a steady drug concentration is ensured within the therapeutic range. The drug dose needed to reach this steady state varies between patients and may change over time, requiring serial valproic acid levels to ensure ongoing appropriate drug dosing. A valproic acid level is generally obtained shortly after initiation of this medication and after dosage adjustments. After serial levels reveal values consistently in the therapeutic range, the valproic acid level may then be monitored at less frequent but regular intervals to ensure that it remains within this range. ^{[1, 2, 4, 3]}

Additional testing of levels may be required if a patient’s condition is not responding to the medication to determine whether the concentration is too low, to determine if the medication is ineffective, or to confirm the patient’s compliance with the medication. A level should also be obtained if a patient develops side effects or complications secondary to valproic acid use. The most common side effects are gastrointestinal effects including anorexia, nausea, and vomiting; however, less frequent but more serious effects on the central nervous system are also reported including sedation, ataxia, and tremor.

Patients using multiple medications, especially other anticonvulsants, may require more frequent evaluation of valproic acid levels due to potential drug interactions. Furthermore, most valproic acid is bound to protein in the blood; however, it is the unbound portion of the drug that is the active component. Therefore, a patient with a condition resulting in lower-than-normal amounts of protein in their blood may be at increased risk of having a supratherapeutic or excess amount of circulating valproic acid and therefore require monitoring of both total and free valproic acid levels. ^{[4, 3]}

Valproic acid (Rx). Available at http://(http://reference.medscape.com/drug/depakote-depakene-valproic-acid-343024).

Valproate Toxicity. Available at http://emedicine.medscape.com/article/819315-overview).

Brunton LL, Chabner BA, Knollmann BC, Goodman & Gilman’s the Pharmacological Basis of Therapeutics. Pharmacotherapy of the Epilepsies, Valproic Acid. 12e. The McGraw-Hill Companies; 2011. Chapter 21.

Valproic Acid: The Test. Available at http://labtestsonline.org/understanding/analytes/valproic-acid/tab/test.

Stern. Drug-Drug Interactions in Psychopharmacology. Massachusetts General Hospital Comprehensive Clinical Psychiatry. Chapter 50.

Stern. Anticonvulsants; PHARMACOKINETICS, PHARMACODYNAMICS, ADVERSE EFFECTS, AND MONITORING. Massachusetts General Hospital Comprehensive Clinical Psychiatry. 1. 1st ed. Chapter 48.

Suzanne Bentley, MD, MPH Assistant Professor, Departments of Emergency Medicine and Medical Education, Icahn School of Medicine at Mount Sinai; Medical Director, Simulation Center at Elmhurst Hospital Center

Suzanne Bentley, MD, MPH is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, American Medical Womens Association, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

Valproic Acid Level 

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