Effect of valproate on the plasma concentrations of aripiprazole in bipolar patients

There is very limited documentation available on the effects of valproate co-medication on the pharmacokinetics of aripiprazole in a naturalistic setting. The aim of the present study was to investigate the effect of co-medication with valproate on serum concentrations of aripiprazole in bipolar disorder patients in a clinical setting.

Plasma samples of bipolar disorder patients (n = 69) on a stable dose of aripiprazole 20 mg/day were analyzed by a liquid chromatography-mass spectrometry method in a routine therapeutic drug monitoring setting. Therapeutic drug monitoring was done for the entire study group before and after valproate co-administration.

We observed a statistically significant difference between the aripiprazole monotherapy and aripiprazole-valproate combination with respect to total aripiprazole plasma levels (p < 0.01). However, no statistically significant differences were noted in aripiprazole levels between the first week and the second week of valproate co-administration.

In conclusion, concurrent treatment with valproate resulted in changes in the total aripiprazole plasma levels by 23%. But a lower total aripiprazole concentration during co-medication with valproate, caused by protein binding displacement, is reported being clinically insignificant in previous studies. The results from these studies are important in order to clarify clinical safety and efficacy.