Serum concentrations of valproic acid: influence of dose and comedication.

The influence of valproate (VPA) dose, VPA preparation used, comedication (phenobarbital, phenytoin, carbamazepine) and factors such as age, weight, height, and sex on the concentration of VPA in serum was investigated. Nonlinear regression analysis showed that about 63% of the variance in the VPA morning concentrations of 259 inpatients could be explained by the following variables: dose, body weight, sex, and comedication. Age, height, and kind of preparation had no important influence on the VPA concentration. The relationship between dose and concentration of VPA is nonlinear, as the concentration does not increase proportionally with the dose but increases to a lesser extent. The serum concentration of VPA is clearly lower when the drug is given in combination with phenytoin (49.5%), carbamazepine (66.2%), or phenobarbital (76.3%) than when given alone (100%).