Abstracts

RATIONALE: The current method of delivery of IV valproic acid (Depacon) involves delivery of modest doses over one hour. A variety of clinical situations exist where rapid attainment of near steady state serum levels would be beneficial. This study sought to determine the safety of infusions of Depacon at rates up to 3.0 mg/kg/min and doses up to 15 mg/kg. METHODS: This was a randomized, parallel-group, multi-center, open-label safety study of patients with epilepsy given Depacon at either 3.0 mg/kg/min or 1.5 mg/kg/min in a 2:1 ratio, at doses up to 15 mg/kg. Inclusion criteria: (1) seizure risk was felt to require more rapid attainment of steady state values of valproic acid than could be obtained from slower infusions, (2) Depacon was indicated, either as initiation or continuation therapy. Blood pressure,heart rhythm, labs, general physical and neurological exams were evaluated. Study of free and total valproic acid levels was performed before and after infusions. RESULTS: 112 patients were treated (40 at 1.5 mg/kg/min, 72 at 3.0 mg/kg/min). Doses of the first infusion averaged 14.4 and 14.7 mg/kg in the two groups. Ages ranged from 13 mos. to 79 yrs. No statistically significant differences were detected between the groups in incidence of any adverse events. No clinically important alterations of blood pressure or rhythm were found, and no clinically significant laboratory abnormalities emerged which were felt by investigators to be due to Depacon. Somnolence, nausea, dyspepsia, dizziness, asthenia and paresthesia were the most common adverse events. The adverse events were transient and generally mild. Peak serum concentrations of valproic acid averaged 96 mcg/mL, and decayed linearly. No serious adverse events were ascribed to Depacon. CONCLUSIONS: Depacon infused at rates up to 3.0 mg/kg/min and doses up to 15 mg/kg was safe and well tolerated by patients of wide range of ages and epilepsy types.