Steady-state pharmacokinetic properties of aripiprazole 10 mg PO g12h in Han Chinese adults with schizophrenia: A prospective, open-label, pilot study.

OBJECTIVES

The aims of this study were to investigate the pharmacokinetic (PK) properties of aripiprazole in the steady state in Han Chinese adults with schizophrenia and to compare them between Han Chinese and white populations described in the literature.

METHODS

This prospective, open4abel, pilot study was conducted at the Mental Health Institute, Xiang-ya Second Hospital, Central South University, Changsha, China. Male and female hospitalized patients aged 18 to 45 years diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-defined schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) total score ⩾60 (indicating schizophrenia of at least mild severity) were eligible. On study days 1 and 2, patients were pretreated with aripiprazole 10 mg PO QD, followed by 10 mg g12h on days 3 to 21. Blood samples were drawn for analysis on day 21 before dosing and 1, 3, 4, 5, 12, 24, 48, 72, 96, 144, and 192 hours after the morning dosing of aripiprazole on day 21. Patients received low-dose (25-100 mg/d) clozapine on day 25 until day 28. The samples were assessed using high-performance liquid chromatography-mass spectrometry and compartment model analysis for aripiprazole. PK properties included mean residence time (MRT) steady-state Cmax (Css max), time to Css max (Tmax), elimination t/12, apparent oral clearance (CL/F), and apparent volume of distribution (V/F). Adverse effects were monitored using physical examination (including vital sign measurements), electrocardiography, electroencephalography, and clinical laboratory testing (including biochemistry, hematology, and urinalysis) at baseline and at the end of the study. Patients were asked about adverse events on days 1 to 7 and at random intervals thereafter. Patients were also instructed to report any spontaneous symptoms they experienced.

RESULTS

Twelve patients were enrolled (6 men, 6 women; mean [SD] age, 26.1 [7.0] years; mean [SD] weight, 56.6 [9.0] kg; mean [SD] PANSS score, 116.8 [12.2]). Aripiprazole exhibited linear kinetic characteristics on a 2-compartment model. After multiple oral doses (10 mg g12h), the mean (SD) t1/2, Css max, Tmax, MRT, V/F, and CL/F were 62.2 (9.0) hours, 557.3 (135.5) ng/mL, 2.6 (1.1) hours, 84.5 (11.2) hours, 173 (48) L, and 1.9 (0.5) L/h, respectively. In Chinese patients, the t/12 values were numerically similar (62.2 [9.0] vs 68.1 [22.9] hours); Css max values were numerically higher (557.3 [135.5] vs 393 [181 ] ng/mL); and V/F and CL/F values were numerically lower (V/F: 173 [48] vs 196 [66] L; CL/F: 1.9 [0.5] vs 3.4 [1.6] L/h) compared with healthy white male volunteers. Adverse effects were mild to moderate: lightheadedness (5 of 12 patients), somnolence (3), tachycardia (3), hypodynamia (2), and extrapyramidal symptoms (EPS) (1). The EPS (convulsive movement of the muscles related to the larynx) led to one patient's discontinuation of the study.

CONCLUSIONS

In this small pilot study of the PK properties of aripiprazole 10 mg PO g12h in Han Chinese patients with schizophrenia, the mean t1/2 value was numerically similar to that previously reported in a population of healthy white male volunteers. However, the mean Css max value was numerically higher, and V/F and CL/F values were numerically lower, compared with those in healthy white male volunteers.