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Test Code VALPG Valproic Acid, Free and Total, Serum

Useful For

Monitoring both total and free valproic acid levels in therapy

 

Assessing compliance

 

Evaluating potential toxicity

Profile Information

Test ID Reporting Name Available Separately Always Performed
VALPF Valproic Acid, Free, S Yes Yes
VALPA Valproic Acid, Tot, S Yes Yes

Method Name

VALPA: Immunoassay

VALPF: Ultrafiltration Followed by Immunoassay

Reporting Name

Valproic Acid, Free and Total, S

Specimen Type

Serum


Specimen Required


Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Specimen Volume: 2 mL

Collection Instructions:

1. Serum gel tubes should be centrifuged within 2 hours of collection.

2. Red-top tubes should be centrifuged and aliquoted within 2 hours of collection.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Serum Refrigerated (preferred) 14 days
  Frozen  28 days
  Ambient  72 hours

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

NA

Icterus

NA

Other

NA

Clinical Information

Valproic acid (valproate, Depakote, or Depakene) is an effective medication for absence seizures, generalized tonic-clonic seizures, and partial seizures, when administered alone or in conjunction with other antiepileptic agents.

 

The valproic acid that circulates in blood is 85% to 90% protein-bound under normal circumstances. In uremia or during concomitant therapy with other drugs that are highly protein-bound (such as phenytoin), valproic acid is displaced from protein, resulting in a higher free fraction of the drug circulating in blood.

 

Since neurologic activity and toxicity of valproic acid are directly related to the unbound fraction of drug, adjustment of dosage based on knowledge of the free valproic acid concentration may be useful in the following situations: concomitant use of highly protein-bound drugs (usually >80% bound), hypoalbuminemia, pregnancy, renal or hepatic failure, and in the elderly. In these situations, the total valproic acid concentration in the blood may underestimate the disproportionately higher free valproic acid fraction.

Reference Values

VALPROIC ACID, TOTAL

Therapeutic: 50 (trough)-125 (peak) mcg/mL

Critical value: ≥151 mcg/mL

 

VALPROIC ACID, FREE

Therapeutic: 5-25 mcg/mL

Critical value: >30 mcg/mL

Interpretation

The generally acceptable range for total valproic acid used as a reference to guide its therapy is 50 to 125 mcg/mL. The corresponding range of free valproic acid concentration for clinical reference is 5 to 25 mcg/mL.

 

Low free valproic acid concentration relative to these ranges may suggest inadequate dosing, while a high free valproic acid concentration may be associated with toxic effects.

 

Because the concentration of valproic acid fluctuates considerably depending on the time from last dose, interpretation of the clinical significance of the valproic acid concentration must take into consideration the timing of the blood specimen. For this reason, 2 collections are sometimes made to assess the trough and peak concentrations.

Clinical Reference

1. Cloyd JC, Fischer JH, Kriel RL, Kraus DM: Valproic acid pharmacokinetics in children: Effects of age and antiepileptic drugs on protein binding and intrinsic clearance. Clin Pharmacol Ther 1993;53:22-29

2. Wagner ML, Graves NM, Leppik IE, et al: The effect of felbamate on valproic acid disposition. Clin Pharmacol Ther 1994;56:494-502

3. Dasgupta A, Volk A: Displacement of valproic acid and carbamazepine from protein binding in normal and uremic sera by tolmetin, ibuprofen, and naproxen: presence of inhibitor in uremic serum that blocks valproic acid-naproxen interactions. Ther Drug Monit 1996;18:284-287

4. Moyer TP: Therapeutic drug monitoring. In Tietz Textbook of Clinical Chemistry. Edited by CA Burtis, ER Ashwood. Fourth edition. WB Saunders Company. Philadelphia, 2005, pp 1237-1285

Day(s) and Time(s) Performed

Monday through Sunday; Continuously

Analytic Time

Same day/1 day

Performing Laboratory

Mayo Medical Laboratories in Rochester

CPT Code Information

VALPA – 80164

VALPF - 80165

LOINC Code Information

Test ID Test Order Name Order LOINC Value
VALPG Valproic Acid, Free and Total, S 57775-9

 

Result ID Test Result Name Result LOINC Value
VALPF Valproic Acid, Free, S 4087-3
VALPA Valproic Acid, Tot, S 4086-5