[Valproic acid toxicity due to misinterpretation of plasma levels: increase in unbound fraction caused by hypoalbuminaemia and renal dysfunction].

BACKGROUND: Valproic acid is one of the most widely prescribed drugs for the treatment of epilepsy and bipolar disorder. As only the unbound fraction of a medicinal product is pharmacologically active, in some strong protein-bound psychotropic drugs such as valproic acid and phenytoin, a rise in this fraction can lead to severe toxicity.

CASE DESCRIPTION: A 65-year-old male with a type 1 bipolar disorder developed a number of neurological symptoms including sluggishness, muscle weakness, difficulty in walking and disorders of micturition after his mood stabiliser was changed to valproic acid. Recognition of drug toxicity was delayed as his total plasma valproic acid levels were within the therapeutic range. Later it became apparent that the patient had toxic unbound valproic acid levels due to hypoalbuminaemia and impaired renal function.

CONCLUSION: Clinicians should always consider drug toxicity in patients who show neurological symptoms and use highly protein-bound psychotropic drugs, even if the total plasma concentration of the drug is in the therapeutic range.