Valproic Acid

Order Code

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3094

Preferred Specimen

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Collect 2 mL of serum. Allow the serum separator tube (SST) to clot in an upright position for at least 30 minutes, then centrifuge within 2 hours after collection. Keep refrigerated.

Container Type

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Serum Separator tube

Alternate Specimen Requirements

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Collect 2 mL of serum from a plain red-top tube. Allow the sample to clot upright for at least 60 minutes, then centrifuge and transfer the serum to a plastic transport tube within 2 hours. Clearly label the tube as serum from a plain red-top tube. Keep refrigerated.

Minimum Volume

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• 0.5 mL Serum

Transport Temperature

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Refrigerated

Expected Turnaround Time

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1 Day

Specimen Stability

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• 5 days at room temperature
• 1 week refrigerated
• 3 months frozen

Methodology

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Roche COBAS homogeneous enzyme immunoassay (EIA).

Overview

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Valproic acid (VAP) is an anticonvulsant used as both mono and adjunctive therapy primarily in the treatment of epilepsy. It is also prescribed for acute mania in bipolar disorder and as prophylaxis for migraine headaches.

To maintain a safe and effective therapeutic range, serial monitoring of VAP levels is recommended. While VAP toxicity often causes mild, reversible central nervous system depression, severe complications and fatalities can occur. Therefore, serum concentrations should be monitored when signs of toxicity appear.

This assay detects total valproic acid. At therapeutic levels, 80–90% of VAP is bound to plasma proteins — only the free fraction is biologically active. Conditions that reduce plasma protein binding (such as advanced age, hepatic or renal dysfunction) can increase free valproic acid levels and risk toxicity.
Certain medications (e.g., high-dose salicylates) can also displace VAP from albumin, increasing the free fraction and potential toxicity.
Patients may show symptoms of VAP toxicity even when total blood levels appear normal. In such cases, free valproic acid testing may help determine the cause. See Valproic Acid Level, Free and Total, Serum

Clinical Significance

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Therapeutic drug monitoring helps assess:

• Poor clinical response
• Signs of toxicity
• Onset of seizures
• Changes in concurrent medications
• Possible noncompliance

Additional Information

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Valproic acid toxicity may result from either acute overdose or chronic therapy (idiosyncratic response). Serum levels do not always reflect toxicity severity.

Common and early symptoms:

• Central nervous system depression (from mild drowsiness/confusion to coma)
• Metabolic issues: hyperammonemia, metabolic acidosis, hyperosmolality, hypernatremia, hypocalcemia
• Hepatotoxicity (acute or chronic)
• Gastrointestinal symptoms: nausea, vomiting, diarrhea
• Rarely, acute pancreatitis

Valproic acid is rapidly absorbed (though food may delay absorption without affecting overall levels). It is extensively metabolized in the liver via glucuronide conjugation and mitochondrial beta-oxidation, with excretion mainly in the urine (2–3% unchanged). The relationship between dose and total valproate concentration is nonlinear.

Drug Interactions

Valproic Acid levels/effects may be increased by:
Alizapride, Azelastine (Nasal), Brimonidine (Topical), Bromopride, Bromperidol, Chlormethiazole, Chlorphenesin Carbamate, ChlorproMAZINE, CloBAZam, Cosyntropin, Dimethindene (Topical), Doxylamine, Droperidol, Esketamine, Felbamate, GuanFACINE, HydrOXYzine, Kava Kava, Lemborexant, LevETIRAcetam, Lisuride, Lofexidine, Magnesium Sulfate, Methotrimeprazine, Metoclopramide, Minocycline (Systemic), Oxomemazine, Perampanel, Primidone, Salicylates, Topiramate, Trimeprazine.

Valproic Acid levels/effects may be decreased by:
Barbiturates, CarBAMazepine, Carbapenems, Cholestyramine Resin, Estrogen Derivatives (Contraceptive), Ethosuximide, Fosphenytoin-Phenytoin, Mefloquine, Methylfolate, Mianserin, Orlistat, Perampanel, Protease Inhibitors, RifAMPin.

References

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Alias

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• depakene (valproic acid)
• depakote

Test Setup Days

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Monday through Friday PM shift

CPT

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80164 LOINC: 4086-5

Reference Range

50.0-125.0 UG/ML
REFERENCE RANGE MAY VARY DEPENDING ON TESTING LOCATION’S
METHODOLOGY

UNIT CODE	UNIT CODE NAME	ANALYTE	GENDER	AGE	REFERENCE RANGE	Units of Measure
3094	VALPRO	VALPRO	NOT SPECIFIED	ALL	50.0–125.0	UG/ML
3094	VALPRO	VALPRO	MALE	ALL	50.0–125.0	UG/ML
3094	VALPRO	VALPRO	FEMALE	ALL	50.0–125.0	UG/ML