[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.

Cigarette smoke inhibits the growth of lung fibroblasts from patients with pulmonary emphysema.

OBJECTIVE: To investigate the proliferative characteristics of fibroblasts cultured from emphysematous lungs. METHODS: Fibroblasts were isolated and cultured from emphysematous lungs surgically resected as a consequence of lung volume reduction surgery and from non-cancerous areas of lungs obtained following resection for lung cancer as a non-emphysematous control. Their proliferative activities were compared, as was the effect of cigarette smoke extract (CSE) on fibroblast proliferation. After incubation with various concentrations of CSE, cells were harvested and cell numbers were counted. Growth curves were constructed and doubling time was calculated to compare the proliferative activity of fibroblasts from emphysematous and non-emphysematous lungs. RESULTS: The proliferation of fibroblasts from emphysematous lungs cultured with normal medium appeared suppressed compared with non-emphysematous lungs. The addition of CSE to the medium induced more obvious growth inhibition in emphysematous lung fibroblasts. The growth of both fibroblast cultures was inhibited by CSE and this appeared to be concentration dependent. CONCLUSIONS: Fibroblasts from emphysematous lungs had lower proliferative activity and were more susceptible to cigarette smoke than those from non-emphysematous lungs. Cigarette smoke may play a critical role in the development and deterioration of pulmonary emphysema by suppressing the growth of lung fibroblasts.