Usefulness of therapeutic drug monitoring of aripiprazole

Purpose: Despite the established efficacy of antipsychotic medication, compliance to treatment is poor, particularly with oral formulation. The emergence of long acting injectable antipsychotic formulations in recent years has aimed to counteract the poor compliance rates observed. Aripiprazole is said to be the most with less side effects antipsychotics. In May 2015, aripiprazole once-monthly 400 mg (AOM 400), an injectable suspension was approved in Japan. However, it is unclear that, in clinical setting, AOM 400 is consistent with therapeutic concentrations observed with oral aripiprazole daily dose. Therefore, in this study, we investigated that the dose of oral aripiprazole to be AOM 400 equivalent was estimated from serum concentration. And more, we make an attempt to explore the influencing factors on the serum concentration of aripiprazole. Methods: Patients who are taking aripiprazole oral and/or AOM 400 for more than one month are subjects. Serum concentration of aripiprazole was measured by high performance liquid chromatography (HPLC). Aripiprazole in serum was extracted by solid extracted method using an Oasis MCX (Waters). The HPLC separation was achieved using an XBridge C18 (250×4.6mm2 i.d., 5mm particle size, Waters) at 25°C. The mobile phase was a mixture (acetonitrile, methanol, 20mM sodium sulfate, and acetic acid were in 27:25:48:1, v/v/v/v). The effluent was monitored with UV detection at 254nm at a flow rate of 1.0 mL/min. A 50mL aliquot was injected into HPLC system. As influencing factors, age, body mass index, hepatic and renal function, triglyceride, total cholesterol, sodium, potassium, and co-medications are listed. All analyses were carried out using SPSS (version 22.0). The influencing factors are calculated by multiple regression analysis. Comparing concentrations were evaluated using the Student's t-test. P<0.05 was considered significant. Results: The average serum concentrations of oral aripiprazole at the dose of 6, 12, 18, 24, and 30 mg were 106.5±31.9, 159.1±73.8, 299.1±108.7, 350.9±150.7, 438.0±162.5 ng/mL, they are dose-dependent manner. The concentration of AOM 400 is 278.6±80.6 ng/mL, it is similar to 18 mg of daily oral dose. The daily dose (P<0.01) and creatinine clearance (P<0.05) are listed as the significant influencing factors on serum concentration of aripiprazole. The concentration was significantly lower (P<0.01) in within carbamazepine (122.9±29.8) compared to without it (407.9±106.2). Conclusion: In this study, it is appeared that the 18 mg of daily oral dose of aripiprazole is consistent with AOM 400 from the view of serum concentration. As influencing factors, dose and creatinine clearance are listed. Since the concentration is dose-dependent manner, it is reasonable that dose would be the candidate. Concurrent with carbamazepine reduces the concentration of aripiprazole. Carbamazepine is an inducer of CYP3A4, and aripiprazole is metabolized by CYP3A4 mainly. Therefore, aripiprazole metabolism would be facilitated. As above, by measuring the serum concentration of aripiprazole, we could provide important information of the medication. This study is small sample, further study is needed.