The influence of other anticonvulsants on the plasma concentration of E-2-en-valproate.

Abstract

E-2-en-valproate is a major metabolite present in the blood of humans treated with valproate. In animals it is a potent anticonvulsant. We have measured concentrations of valproate and E-2-en-valproate in 102 plasma samples obtained from 75 adult patients (20 taking valproate only; 55 taking valproate and other anticonvulsants) under steady-state conditions. The two groups' mean ages and weights were comparable. The average valproate daily dose was lower (p < 0.002) in the monotherapy group (1152 +/- S.D. 661 mg/d) than in the polypharmacy group (1902 +/- S.D. 874 mg/d). Despite this, the mean plasma levels of valproate and E-2-en-valproate were significantly higher (p < 0.05, p < 0.0001, respectively) in the monotherapy group (60.0 +/- S.D. 22.6 micrograms/ml; 3.00 +/- S.D. 1.40 micrograms/ml, respectively) than in the polypharmacy group (49.5 +/- S.D. 24.8 micrograms/ml; 1.73 +/- S.D. 0.95 microgram/ml). While the mean plasma valproate level was 17.5% lower in the polypharmacy group, the mean plasma E-2-en-valproate level was 42% lower. The co-administration of other anticonvulsants significantly reduced the concentration of valproate and, more so, of E-2-en-valproate in plasma.