Quantitative levels of aripiprazole parent drug and metabolites in urine

OBJECTIVE: The aim of this study is to assess urine levels of aripiprazole and metabolites among patients receiving steady-state dosing of aripiprazole. METHODS: One hundred fifty adults, judged compliant with a stable aripiprazole regimen, had observed dosing for 5 consecutive days. Urine specimens, obtained on days 1, 4, and 5, were analyzed for pH, creatinine, specific gravity, and for aripiprazole, OPC3373, and dehydroaripiprazole. Linear regression was used to assess the association between unadjusted urine levels of each drug/metabolite and dose taken, and linear stepwise multiple regression was performed to identify variables that added to the explanation of the variance. RESULTS: OPC3373 was found in 97 % of urine samples, whereas unchanged aripiprazole and dehydroaripiprazole were found in only 58 and 39 % of samples, respectively. Variance in urine metabolite levels accounted for by medication dose was relatively low for each individual drug/metabolite, r (2) only 0.13 to 0.23. However, when OPC3373 was adjusted for age, weight, sex, and urine creatinine values, the r (2) improved to 0.63, and further improved to 0.70, when height, urine specific gravity, and the presence of dehydroaripiprazole were added in a stepwise multiple regression model. CONCLUSIONS: Unadjusted urine levels of aripiprazole and metabolites are not strongly related to aripiprazole dosing, however, accounting for key variables yields a strong relationship between measurable urine parameters and dose taken. By defining the expected range of adjusted urine levels for each dose, the potential exists for a clinical test to identify partially nonadherent individuals who would not have been identified by conventional “present vs. absent” urine drug testing.