Safety of high intravenous valproate loading doses in epilepsy patients

Parenteral antiepileptic drugs (AEDs) are required in patients needing emer gent treatment or unable to take oral medication. Ln the two United States trials of TV valproate, only low therapeutic serum levels were achieved. Th is study evaluated the safety of high loading doses to achieve therapeutic levels rapidly. Twenty-five epilepsy patients without active seizures recei ved a single loading dose of TV valproate (Depacon) based on body weight an d infused over 1 hour. Ages were 4-39 years (mean: 13.1 +/- 8.6 years). Ele ctrocardiogram (ECG) and electroencephalogram (EEG) were monitored througho ut infusion; blood pressure was measured before and after. Serum valproate was measured 10 minutes postinfusion. The TV valproate dose range was 15-44 mg/kg (mean: 28.3 +/- 7.4 mg/kg); infusion rates were 0.25-0.73 mg/kg/minu te (mean: 0.47 +/- 0.1 mg/kg/minute). Postinfusion serum valproate concentr ations were 71-277 mu g/ml (mean: 135.3 +/- 59.5 mu g/ml). There were no si gnificant changes in blood pressure, no redness or tenderness at the IV Sit e, and no ECG abnormalities. One patient with Serum valproate greater than or equal to 200 mu g/ml had mild sedation (resolving in 24 hours). We concl uded that serum valproate concentrations of greater than or equal to 100 mu g/ml can be achieved rapidly and safely parenterally, a finding with impor tant implications for the treatment of status epilepticus. (C) 1998 by Else vier Science inc. All rights reserved.