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Unit Code 8707:
Valproic Acid, Total, Serum

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Useful For

Monitoring therapy

 

Assessing compliance

 

Evaluating potential toxicity

Clinical Information

Valproic acid is used for treatment of simple and complex absence

seizures and as combination therapy with other anticonvulsants

for control of generalized seizures that include absence seizures.

Valproic acid is initially dosed at 15 mg/kg/day, with dosage

increases over time to a maximum of 60 mg/kg/day.

 

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.

 

The volume of distribution of valproic acid is 0.2 L/kg and its

half-life is 10 to 14 hours in adults, and shorter in children. It is

approximately 90% protein bound.

 

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-fold to 3-fold mass excess and a

5-fold to 7-fold molar excess.

 

Major side effects such as central nervous system depression,

thrombocytopenia, and hepatic dysfunction are likely to be

experienced if the peak level regularly is >125 ug/mL.

Reference Values

Therapeutic concentration:  40 (trough)-100 (peak) ug/mL

Toxic concentration:  > or =120 ug/mL

Interpretation

Optimal response is usually observed when the trough level is >40 ug/mL.

 

Peak levels should not be >100 ug/mL.

Cautions

No significant cautionary statements

Clinical Reference

1. Cotariu D, Zaidman JL:  Valproic acid and the liver. Clin Chem

     1988;34:890-897

 

2. Moyer TP:  Therapeutic Drug Monitoring. In: Burtis CA, Ashwood ER,

     Tietz Textbook of Clinical Chemistry. 4th edition. Philadelphia, WB

     Saunders Company 2005 pp 1237-1285

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