Large variability of aripiprazole and dehydroaripiprazole serum concentrations in adolescent patients with...

Aripiprazole is a fairly new atypical antipsychotic substance. It acts as a partial D2- and 5-HT1A-agonist and as a 5-HT2A-antagonist. To date, there are few data concerning the dose-serum concentration relationship in children and adolescent psychiatric patients. Also, there are only few data on the influence of age, sex, body mass index, smoking behavior, and comedication on aripiprazole serum concentrations. In 33 consecutively admitted patients of a child and adolescent psychiatric hospital [age (mean +/- standard deviation) 18.7 +/- 1.7 years (range, 13.5-21.6 years)], 117 steady-state serum concentrations (repeated samples from individuals) of aripiprazole and its metabolite dehydroaripiprazole were assessed using high-performance liquid chromatography. The aripiprazole (mean +/- standard deviation) daily dose was 12.9 +/- 6.4 mg (range, 5-30 mg); the aripiprazole serum concentration was 142.0 +/- 122.7 ng/mL (range, 40.0-648.3 ng/mL; interquartile range, 74.0-167.0 ng/mL). The mean dehydroaripiprazole serum concentration was 51.6 +/- 22.3 ng/mL (range, 30.0-111.6 ng/mL; interquartile range, 34.3-62.1 ng/mL). There was a positive correlation between oral dose and serum concentrations of aripiprazole (r = 0.548, P = 0.001) and dehydroaripiprazole (r = 0.740, P < 0.0005). Aripiprazole serum concentrations showed high inter- and intraindividual variability. Intraindividual variability was one- to 9.3-fold (dehydroaripiprazole: one- to 8.6-fold) and maximum interindividual variability 6.4-fold (dehydroaripiprazole: 6.8-fold). No significant influence was detected for age, sex, body mass index, comedication, and smoking on concentration-to-dose aripiprazole serum concentrations. Further studies are required to obtain data on the relationship between serum concentrations and resulting clinical effects.