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HelpTest 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, SSpecimen Type
SerumSpecimen Required
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
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 the serum aliquoted into a plastic vial within 2 hours of collection.
Specimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Refrigerated (preferred) | 14 days | |
| Frozen | 28 days | ||
| Ambient | 72 hours |
Reject Due To
| Gross hemolysis | Reject |
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: concomitant use of highly protein-bound drugs (usually >80% bound), hypoalbuminemia, pregnancy, kidney or liver failure, and in older adults. 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 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, whereas 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.
Cautions
Specimens subjected to significant heat or other factors that could cause protein denaturation would demonstrate an artificially increased free valproic acid.
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: Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry. 4th ed. WB Saunders Company; 2005:1237-1285
5. Patsalos PN, Spencer EP, Berry DJ: Therapeutic drug monitoring of antiepileptic drugs in epilepsy: A 2018 update. Ther Drug Monit. 2018 Oct;40(5):526-548. doi: 10.1097/FTD.0000000000000546
Method Description
The assay is based on a homogeneous enzyme immunoassay technique used for the quantitative analysis of valproic acid (free and protein-bound) in human serum or plasma. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PD) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD+) to NADH, resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PD does not interfere because the coenzyme functions only with the bacterial (Leuconostoc mesenteroides) enzyme employed in the assay.(Package insert: Valproic Acid reagent. Roche Diagnostics; 04/2018)
Day(s) Performed
Monday through Sunday
Report Available
Same day/1 daySpecimen Retention Time
1 weekPerforming Laboratory
Mayo Clinic 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 |
Forms
If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.