[Pharmacokinetics and safety of aripiprazole long-acting injection, following multiple deltoid administrations in schizophrenia patients in Japan].

Aripiprazole once-monthly (AOM) was previously approved for treatment of schizophrenia as monthly injections in the gluteal muscle. The deltoid muscle provides a more accessible injection site. The present study was conducted in Japanese schizophrenia patients as a 24-week, open-label trial that assessed the pharmacokinetics and safety of 5 sequential doses of AOM 400 mg (AOM 400) once every 4 weeks administered in the deltoid muscle. Patients treated with an oral atypical antipsychotic (other than aripiprazole) continued to receive their pre-study medication up to 14 days after the first AOM 400 injection. The completion rate was 76.5% (n = 13/17). Mean aripiprazole plasma C(min) almost reached steady-state by the fourth AOM 400 injection. After the fifth AOM 400 injection, mean aripiprazole AUC(28d), C(max) and C(min) were 165 µg x h/ml, 331 ng/ml and 201 ng/ml, respectively, which were similar to previously published pharmacokinetic parameters after the fifth gluteal injection of AOM 400. The most common treatment-emergent adverse event (TEAE) was injection site pain (35.3%). Most TEAEs were classified as mild in intensity. In conclusion, the deltoid injection of AOM can be considered an alternative route of administration, as deltoid and gluteal injections are interchangeable in terms of aripiprazole plasma concentrations, with no additional safety issues.

Detection of endothelial progenitor cells in human skin wounds and its application for wound age determination.

Endothelial progenitor cells (EPCs), a newly identified cell type, are bone marrow-derived progenitor cells that co-express stem cell markers and vascular endothelial growth factor (VEGF) receptor (Flk-1). In this study, a double-color immunofluorescence analysis was carried out using anti-CD34 and anti-Flk-1 antibodies to examine the time-dependent appearance of EPCs, using 52 human skin wounds with different wound ages (Group I, 0-1 days; Group II, 2-6 days; Group III, 7-14 days; and Group IV, 17-21 days). In wound specimens with an age of less than one day, CD34(+)/Flk-1(+) EPCs were not detected. EPCs were initially observed in wounds aged two days, and their number was increased in lesions with advances in wound age. In morphometrical analysis, the average number of EPCs was the highest in the wounds of Group III. Especially, 20 out of 21 wounds aged 7-12 days had >20 EPCs, and all wound samples with postinfliction intervals of 14-21 days had <15 EPCs. These observations at least showed that >20 EPCs would indicate a wound age of 7-12 days. Taken together, our observations indicate the detection of EPCs would be useful for wound age determination.