A multivariable analysis of factors governing the steady-state pharmacokinetics of valproic acid in 52 young epileptics.

A number of factors have been implicated in the interpatient variability of valproic acid (VPA) pharmacokinetics. These include patient age, concurrent anticonvulsant therapy, and dosage of VPA. In the clinical setting, it is important to determine which of these variables exert a major effect on the observed differences in VPA disposition. Accordingly, we analyzed the data from 52 young epileptic patients using multivariate statistical methods. Concurrent anticonvulsant therapy was the major determinant of VPA clearance in this patient population. The half-life of VPA was significantly related to age, but volume of distribution and clearance were not. The dosage of VPA affected the volume of distribution of VPA but not the half-life or clearance of this drug. These results provide a more rational understanding of VPA pharmacokinetics in the clinical setting and have implications for the monitoring and manipulation of VPA therapy in the epileptic population.