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HelpMayo Test ID VALPA Valproic Acid, Total, Serum
Specimen Required
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 0.5 mL
Collection Instructions:
1. Serum gel tubes should be centrifuged within 2 hours of collection.
2. Red-top tubes should be centrifuged and serum aliquoted into a plastic vial within 2 hours of collection.
Useful For
Monitoring total valproic acid in therapy
Assessing compliance
Evaluating potential toxicity
Method Name
Immunoassay
Reporting Name
Valproic Acid, Tot, SSpecimen Type
SerumSpecimen Minimum Volume
0.25 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.
Valproic acid is initially dosed at 15 mg/kg/day, with dosage increases over time to a maximum of 60 mg/kg/day. The volume of distribution of valproic acid is 0.2 L/kg, and its half-life is 10 to 14 hours in adults but is shorter in children. It is approximately 90% protein bound.
Hepatic failure and a Reyes-like syndrome associated with administration of valproic acid at therapeutic levels have been reported. Careful monitoring of liver function during the first 6 months of therapy is required. Major side effects such as central nervous system depression, thrombocytopenia, and hepatic dysfunction are likely to be experienced if the peak level is regularly above 125 mcg/mL.
Analysis of free valproic acid levels may be useful in delineating the cause of toxicity when the total concentration is not excessive.
Valproic acid exhibits substantial effects on the pharmacology of phenytoin, whereas phenytoin exhibits only a limited effect on valproic acid. This is due to the relative abundance of the 2 drugs in the body. Valproic acid is present at a 2- to 3-fold mass excess and a 5- to 7-fold molar excess.
Reference Values
Therapeutic: 50 (trough)-125 (peak) mcg/mL
Critical value: ≥151 mcg/mL
Interpretation
The generally acceptable range for total valproic acid used as a reference to guide therapy is 50 to 125 mcg/mL. Peak levels should not exceed 125 mcg/mL.
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
No significant cautionary statements
Clinical Reference
1. Cotariu D, Zaidman JL: Valproic acid and the liver. Clin Chem. 1988 May;34(5):890-897
2. Langman LJ, Bechtel LK, Meier BM, Holstege C: Clinical toxicology. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:832-887
3. Milone MC, Shaw LM: Therapeutic Drug Monitoring. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics. 8th ed. Saunders; 2019:549
4. Patsalos PN, Zugman M, Lake C, James A, Ratnaraj N, Sander JW. Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: a comparison of free non-protein-bound concentrations. Epilepsia. 2017 Jul;58(7):1234-1243. doi: 10.1111/epi.13802
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 to 2 daysSpecimen Retention Time
1 weekPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.CPT Code Information
80164
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| VALPA | Valproic Acid, Tot, S | 4086-5 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| VALPA | Valproic Acid, Tot, S | 4086-5 |