Reduction of Steady‐State Valproate Levels by Other Antiepileptic Drugs

Abstract

Steady-state plasma valproate (VPA) levels were analyzed in 37 children after 6 wk of VPA therapy. Patients (26) were receiving other antiepileptic drugs in addition to VPA (experimental group). Eleven patients who received VPA alone served as controls. The mean VPA dose was not statistically different for the 2 groups (experimental group, 35.4 mg/kg per day, 11.6 SD; control group, 31.1 mg/kg per day, SD 6.6). The mean plasma VPA level was significantly lower for the experimental group (63.0 .mu.g/ml, SD 21.8) than for the control (99.3 .mu.g/ml, SD 23.3). VPA level:dose ratio (LDR) was also reduced in the experimental group (1.92, SD 0.75) as compared to controls (3.26, SD 0.65). Within the experimental group the VPA levels and VPA LDR were significantly reduced in patients receiving either phenytoin or phenobarbital. Other antiepileptic drugs may significantly alter the steady-state level to dose relationship for VPA.