Three Patients Needing High Doses of Valproic Acid to Get Therapeutic Concentrations

الملخص EN

Valproic acid (VPA) can autoinduce its own metabolism.

Cases requiring VPA doses >4000 mg/day to obtain therapeutic plasma concentrations, such as these 3 cases, have never been published.

Case 1 received VPA for seizures and schizophrenia and had >50 VPA concentrations in 4 years.

A high dose of 5,250 mg/day of VPA concentrate was prescribed for years but this dose led to an intoxication when switched to the enterocoated divalproex sodium formulation, requiring a normal dose of 2000 mg/day.

VPA metabolic capacity was significantly higher (t=-9.6; df = 6.3, p<0.001) during the VPA concentrate therapy, possibly due to autoinduction in that formulation.

Case 2 had VPA for schizoaffective psychosis with 10 VPA concentrations during an 8-week admission.

To maintain a VPA level ≥50 μg/mL, VPA doses increased from 1500 to 4000 mg/day.

Case 3 had tuberous sclerosis and epilepsy and was followed up for >4 years with 137 VPA concentrations.

To maintain VPA concentrations ≥50 μg/mL, VPA doses increased from 3,375 to 10,500 mg/day.

In Cases 2 and 3, the duration of admission and the VPA dose were strongly correlated (r around 0.90; p<0.001) with almost no change after controlling for VPA concentrations, indicating progressive autoinduction that increased with time.