Valproic acid (VPA) is a widely prescribed broad-spectrum antiepileptic drug. However, the use of VPA is complicated in clinical practice by its remarkably wide variability of pharmacokinetics. The objective of this study was to investigate the effects of demographic factors and associated therapies on steady-state plasma VPA concentrations in patients with epilepsy.

This retrospective cohort study was carried out using the routine therapeutic drug monitoring (TDM) database. Stepwise logistic regression analysis was used to compare serum VPA levels in 78 epilepsy patients treated with VPA in association with at least one other drug that could have interacted with CYP2C9, CYP2C19 or UGT enzymes.

The frequency of subtherapeutic serum VPA levels was significantly increased with younger age (P<0.02), the number of co-medications (P<0.007) and use of enzyme-inducing co-medications (P<0.02). No significant correlations between VPA dose and trough plasma concentrations were found, as the latter did not increase in proportion to the dose.

Routine monitoring of VPA serum levels would be extremely useful in epilepsy patients in the pediatric age group and in those who require associated enzyme-inducing medications.