What is the therapeutic range for valproic acid?

• A. 25-50 mcg/mL
• B. 50-125 mcg/mL
• C. 100-200 mcg/mL
• D. 150-300 mcg/mL

Answer: (B)

Therapeutic drug monitoring is used with valproic acid because it has a variable pharmacokinetic profile and a narrow window between effective seizure control and toxicity. For most adults, keeping total valproic acid in the range of about 50 to 125 mcg/mL provides reliable seizure control with an acceptable risk of adverse effects. Levels below this range may be ineffective, while levels above this range increase the chance of toxicity such as liver injury, low platelet counts, pancreatitis, and sedation. Since valproic acid is highly protein-bound, the measured total concentration can be affected by albumin levels; in patients with low albumin or organ dysfunction, the free, active fraction can be higher, which may require monitoring free levels or adjusting the dose.