Valproate level (Valproic acid)

Sample

1. This is done on the serum of patients (mostly epileptics).
2. The best time is before the second dose.
3. The other best time is early in the morning.

Purpose of the test (Indications)

• This is done on patients who are on Valproic acid drug treatment.
• This monitors the dose and prevents toxic levels.
• This is done in the patient with Epilepsy.

The complication of Valproic acid (antiepileptic drug):

1. Valproic acid may cause serious or life-threatening damage to the liver.
2. Anticonvulsant drugs like phenobarbital were used for epilepsy and this may lead to:
   1. Drowsiness.
   2. Fatigue.
   3. Depression.
   4. Decreased mental capacity.
3. Valproic acid has a great risk in children under the age of 2 years.
   1. Valproic acid absorption from GIT is rapid and complete.
   2. It is eliminated by liver metabolism.
   3. Circulating valproic acid is highly protein-bound almost 93%.
   4. The percentage of protein-bound decreases in:
      1. Renal failure.
      2. In late liver diseases.
      3. Drugs that compete for its binding sites.
4. Valproic acid is used to control tonic-clonic and partial seizures.
5. Avoid other medications when the patient is taking valproic acid.
6. The mechanism of the valproic acid is that it inhibits GABA transaminase, resulting in an increase in the concentration of  GABA in the brain.
   1. GABA is the potent inhibitor of presynaptic and postsynaptic discharge in the brain.

1. 2. This acid modulates the synaptic sodium by prolonging inactivation, which decreases the ability of the neurons to respond at high frequency.
2. Valproic acid is rapidly absorbed from the GIT after the oral intake.
   1. The peak level is 1 to 4 hours after the oral dose.
   2. The half-life is 16 hours but it decreases in 12 hours after the therapy.
   3. In the case of long-term therapy, it decreases in 8 hours.

1. 

   Level of Valproic acid in the blood

   4. Valproic acid dose >100 µg /mL is hepatotoxic and leads to acute hepatic encephalopathy.
      1. The dose should be adjusted to 40 µg /mL to 100 µg /mL.
      2. The best time to get a blood sample is before the next dose.
   5. The patient may develop complications:
      1. Excessive tiredness,
      2. There is a lack of energy.
      3. The patient may develop weakness.
      4. There is a stomach pain.
      5. There is a loss of appetite, nausea, vomiting, or swelling of the face.
      6. This may cause damage to the pancreas.
   6. Level >200 µg/mL may show:
      1. Pancreatitis.
      2. Hallucination.
      3. Raised ammonia level (Hyperammonemia).
   7. Hepatic dysfunction may happen even at a therapeutic level. So regularly check the liver function tests.
      1. Initially check frequently liver functions in the first 6 months of therapy.
   8. Valproic acid can cause birth defects in pregnant women.
   9. The goal of epilepsy treatment is:
      1. Seizure control.
      2. Epilepsy control.
      3. Ultimately reversal of the disease.
   10. Evaluation of the free or nonbound fraction is a more reliable index of a therapeutic or toxic dose.

   Therapeutic level is

   • 50 to 120 µg/mL.
   • Another source
     • 50 to 120 µg/mL.

   Toxic level is

   • > 200 µg/mL.

Another source 2

Toxic level = >100 µg/mL.

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