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Laboratory: Clinical Biochemistry  (HSC ONLY - AUTO)
Test Name:
VALPROIC ACID, TOTAL AND FREE (Alternate Name(s): Depakote, Depakene) - (S)
Test Code: FVAL
Clinical Information:
Valproic acid is an anticonvulsive and mood stabilizer medication.
This test is used for monitoring both total and free valproic acid in patients with renal failure or during concomitant therapy with other drugs that are also highly protein-bound (e.g. phenytoin).
In uremia, or during therapy with other protein-bound drugs (e.g. phenytoin), valproic acid is displaced from protein, resulting in a higher free fraction of circulating drug. Neurologic activity and toxicity are directly related to the free fraction. As a result, measurement of free valproic acid level is the best indicator to determine adequate therapeutic level or toxicity.
Collection Devices:
Specimen Required:
Serum: 1.5 mL
Pediatric Serum: 1.5 mL

Trough measurements are recommended (within 30 minutes before next dose).
Allow serum specimen to clot completely at room temperature to ensure complete clot formation has taken place prior to centrifugation. Centrifuge and aliquot within 2 hours of collection.
Stability: 14 days refrigerated, 28 days frozen

Shipping & Storage: Send refrigerated or frozen serum to HSC-MS5 for testing.
Attach original requisition
Address to HSC Auto Chem
Testing Laboratory (MB): HSC (Health Sciences Centre) – Biochemistry. All testing performed at HSC Auto Chem. 
Reference Values:
Total Valproic Acid
Therapeutic (Trough):   50-100 mg/L
Toxic:              >120 mg/L 

Free Valproic Acid
Therapeutic (Trough):   5-10 mg/L
Toxic:              >10 mg/L

Method of Analysis: Ultrafiltration & Homogeneous enzyme (G6PDH) immunoassay (Roche Cobas)
See Also:
More Information:
The plasma protein binding of valproate is saturable within the typical therapeutic range (approximately 90% at 75 mg/L or 520 µmol/L). With a daily dose of more than 500 mg, plasma concentrations may not increase proportionately as clearance increases with an increase in the free fraction.
Daily fluctuations (up to two times higher) in free fraction and clearance also occur as a result of displacement by free fatty acids or circadian influences; thus, when plasma concentrations are being monitored, samples should be drawn at a uniform time. Monitoring of trough concentrations is recommended by neurologists.

Interpretation & Assay Interferences:
Half-life: 8-60 hours (dose dependent)
Time to steady state: 2-13 days