Reduction of steady-state valproate levels by other antiepileptic drugs.

Steady-state plasma valproate (VPA) levels were analyzed in 37 children after 6 weeks of VPA therapy. Twenty-six patients 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 two groups (experimental group, 35.4 mg/kg/day, 11.6 SD; control group, 31.1 mg/kg/day, SD 6.6) The mean plasma VPA level was significantly lower for the experimental group (63.0 micrograms/ml, SD 21.8) than for the control (99.3 micrograms/ml), SD 23.3) (p less than 0.01). 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) (p less than 0.01). Within the experimental group the VPA levels and VPA LDR were significantly reduced in patients receiving either phenytoin or phenobarbital. The data suggest that other antiepileptic drugs significantly alter the steady-state level to dose relationship for VPA.