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Background and Objective: Inadequate response to antidepressant monotherapy is common among patients with major depressive disorder (MDD). The efficacy and safety of adjunctive brexpiprazole 2 mg/day has recently been confirmed during the 6-week, randomized, placebo-controlled phase 2/3 (BLESS) study, which evaluated brexpiprazole at 1 mg/day and 2 mg/day versus placebo as adjunctive therapy to antidepressant therapies in 740 Japanese patients with MDD and an inadequate response to antidepressant monotherapy. This study evaluated the long-term safety and efficacy of adjunctive fixed-dose brexpiprazole 2 mg/day in Japanese patients with MDD., Methods: An open-label, 52-week study enrolled rollover patients who completed the 6-week, double-blind, randomized, placebo-controlled phase 2/3 BLESS study (NCT03697603), and de novo patients aged ≥ 65 years. Patients were titrated to fixed-dose brexpiprazole 2 mg/day from Week 1. Safety assessments included treatment-emergent adverse events (TEAEs; primary outcome) and clinical and laboratory variables. Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression-Improvement (CGI-I) scale, Hamilton Depression Rating Scale (HAM-D) 17-item total score, and Sheehan Disability Scale (SDS) score., Results: In total, 247 patients [rollover, n = 216; de novo (previously unexposed), n = 31] were included in the safety/efficacy populations, and 138 (rollover, n = 132; de novo, n = 6; 55.9%) completed the study. Common TEAEs (incidence ≥ 10%) were weight gain [33.2% (n = 82)], akathisia [23.5% (n = 58)], nasopharyngitis [21.1% (n = 52)], and somnolence [10.5% (n = 26)]. TEAEs leading to treatment discontinuation occurred in 26.7% of patients receiving brexpiprazole and 58.1% of de novo patients. The mean (SD) increase in body weight from baseline to Week 52 [observed cases (OC)] was 4.2 (6.5) kg (n = 138); 44.5% (n = 110) had weight gain ≥ 7% at any postbaseline visit. There were no cases of tardive dyskinesia and no AEs related to suicide/suicide attempts. One death occurred (unknown cause), which was unrelated to study treatment. Improvements in the MADRS total score were observed from baseline over the course of the 52-week study [mean (SD) change at Week 52 (OC): - 7.3 (8.7)] for all patients receiving brexpiprazole. The overall MADRS response rate and remission rate in patients receiving brexpiprazole was 41.3% (n = 57) and 34.8% (n = 48), respectively, at Week 52 (OC). Improvements in CGI-S, HAM-D 17 item total score, and SDS mean scores were also observed from baseline over the 52-week study, with a mean (SD) change from baseline at Week 52 (OC) of - 0.8 (1.0), - 5.9 (6.3), and - 1.0 (2.2), respectively, indicating a sustained improvement in symptoms with long-term brexpiprazole treatment., Conclusions: This is the first study to evaluate the safety profile of brexpiprazole 2 mg/day in Japanese patients with MDD, including older adults, which is similar to previous reports, with no new safety risks, and continued efficacy over 52 weeks., Study Registration: ClinicalTrials.gov (NCT03737474; registered on 29 July 2018)., (© 2024. The Author(s).)

Background: Rebamipide has been widely co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) in Japan for decades. This study aimed to evaluate the effectiveness of rebamipide in preventing upper gastrointestinal bleeding in new users of NSAIDs without risk factors of NSAID-induced ulcers other than age., Methods: A nested case-control study was conducted using medical claims data of 1.66 million inhabitants of 17 municipalities participating in Japan's Longevity Improvement & Fair Evidence study. The cohort entry (t0) corresponded to a new user of NSAIDs for osteoarthritis or low back pain. Patients with risk factors of NSAID-induced ulcers other than age were excluded. Cases were defined as patients who underwent gastroscopy for upper gastrointestinal bleeding (occurrence date was defined as index date). A maximum of 10 controls were selected from non-cases at the index date of each case by matching sex, age, follow-up time, and type and dosage of NSAIDs. Exposure to rebamipide was defined as prescription status from t0 to index date: Non-user (rebamipide was not co-prescribed during the follow-up period), Continuous-user (rebamipide was co-prescribed from t0 with the same number of tablets as NSAIDs), and Irregular-user (neither Non-user nor Continuous-user). Conditional logistic regression analysis was conducted to estimate each category's odds ratio compared to non-users., Findings: Of 67,561 individuals who met the inclusion criteria, 215 cases and 1,516 controls were selected. Compared with that of Non-users, the odds ratios and 95% confidence interval were 0.65 (0.44-0.96) for Continuous-users and 2.57 (1.73-3.81) for Irregular-users., Conclusions: Continuous co-prescription of rebamipide significantly reduced the risk of upper gastrointestinal bleeding in an Asian cohort of new users of NSAIDs with osteoarthritis or low back pain without risk factors other than age., Competing Interests: Authors with competing interests I have read the journal’s policy and the authors of this manuscript have the following competing interests:Yasuharu Nakashima received research grants from Chugai Pharmaceutical Co., Ltd., AYUMI Pharmaceutical Corporation, EA Pharma Co., Ltd., KYOCERA Corporation, and Zimmer Biomet G.K. All other authors have no conflicts of interest to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Yamate et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To determine the long-term safety of switching to brexpiprazole from aripiprazole or non-aripiprazole dopamine antagonists., Methods: Post-hoc analysis of 56-week study of Japanese outpatients with schizophrenia switched to brexpiprazole 2 mg/day over 4-week switching period with further titration (1-4 mg/day) allowed during the 52-week, open-label period. Major assessment items: total/low-density lipoprotein (LDL)-/high-density lipoprotein (HDL)-cholesterol, triglycerides, blood glucose, body weight and prolactin. Secondary evaluations were related to efficacy, treatment emergent adverse events (TEAEs), extrapyramidal symptoms, and corrected QT interval (QTc)., Results: 84/186 (45.2%) patients (aripiprazole, 32.9%; non-aripiprazole, 54.8%) discontinued treatment over 56 weeks mainly because of consent withdrawal/adverse events. From baseline to Week 56, both groups showed minimal mean changes in total/LDL-/HDL-cholesterol, triglycerides, and glucose levels and a slight increase in mean (SD) body weight (aripiprazole, 1.1 [4.4] kg; non-aripiprazole, 0.4 [4.6] kg). Mean prolactin levels increased slightly in the aripiprazole group, but decreased in the non-aripiprazole group. Symptom severity scores decreased similarly in both groups. TEAEs occurred in 161/186 (86.6%) patients (aripiprazole, 84.1% [serious, 9.8%]; non-aripiprazole, 88.5% [serious, 14.4%]). Few changes occurred in extrapyramidal symptom scales or QTc interval., Conclusions: Switching to brexpiprazole is associated with a low long-term risk for metabolic abnormalities (including weight gain), hyperprolactinemia, extrapyramidal symptoms and QTc changes and minimal changes in psychiatric symptoms., (© 2021 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons Ltd.)

A post hoc analysis was performed using data obtained over eight weeks from 200 Japanese patients with schizophrenia who were switched to brexpiprazole monotherapy in a long-term treatment study. The 8-week period comprised of a 4-week switching phase and a 4-week post-switch phase. For the antipsychotic switching schedule, brexpiprazole was first administered at 1 mg/day and increased to 2 mg/day by the end of week 4. Concurrently, the previous antipsychotic(s) was/were tapered gradually from the start of week 3 and discontinued by the end of week 4. Brexpiprazole could then be increased up to 4 mg/day according to the CGI-I criteria. At week 8, 1.8%, 23.2%, 25.0%, and 50% of patients were administered daily brexpiprazole doses of 1, 2, 3, and 4 mg, respectively. The discontinuation rate at week 8 was 17.0%. The major reasons for discontinuation were consent withdrawal (9.5%), occurrence of adverse events (5.5%), and physician's decision (2.0%). Commonly reported adverse events were nasopharyngitis (13.5%), schizophrenia (9.0%), insomnia (6.5%), headache (5.5%), and akathisia (5.5%). The discontinuation rate was 4.9% for patients who were switched from aripiprazole as the primary antipsychotic and 25.4% for those who were switched from other antipsychotics. Owing to the serious adverse events that led to treatment discontinuation, careful switching to brexpiprazole is necessary in patients who previously used olanzapine as their primary antipsychotic., (© 2020. Otsuka Pharmaceutical Co Ltd. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Oral treatment for elderly outpatients with pneumonia is becoming increasingly important in this super-aged society from the perspective of cost-effectiveness and limited hospital capacities. We evaluated the efficacy and safety of two oral respiratory quinolones, sitafloxacin and garenoxacin, in elderly patients with pneumonia. This randomized, multicenter, open-label trial was conducted among patients aged ≥65 years with clinically and radiographically confirmed pneumonia in Japan. Patients were randomly assigned (1:1) to receive either sitafloxacin (100 mg/day) or garenoxacin (400 mg/day) for 3-10 days. The primary efficacy endpoint was the clinical cure rate at 5-10 days after the end of treatment. From December 2013 to November 2017, we enrolled 120 patients at 11 hospitals and randomly assigned 59 patients to the sitafloxacin group (1 patient withdrew) and 61 patients to the garenoxacin group. These included 30 patients with nursing and healthcare-associated pneumonia (NHCAP) (18 receiving sitafloxacin, 12 receiving garenoxacin) and 37 patients with aspiration pneumonia (16 receiving sitafloxacin, 21 receiving garenoxacin). The clinical cure rates in the sitafloxacin and garenoxacin groups were 88.5% (95% confidence interval: 76.6-95.6) and 88.9% (95% confidence interval: 77.4-95.8), respectively. No significant differences were observed in the incidence rates of drug-related adverse events between the sitafloxacin (20.7%; 12/58 patients) and garenoxacin (27.9%; 17/61 patients) groups. The most common adverse event was hepatic dysfunction, which occurred in seven patients in each group. We conclude that sitafloxacin and garenoxacin are comparably effective and safe for the treatment of pneumonia, including NHCAP and aspiration pneumonia, in elderly patients., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Brexpiprazole (Rxulti ® , Rexulti ® ) is an oral atypical antipsychotic agent approved for the treatment of schizophrenia in the EU (in adult patients) and the USA, as well as in some other countries, including Japan. Like aripiprazole, it is a partial agonist at dopamine D 2 and serotonin 5-HT 1A receptors and an antagonist at serotonin 5-HT 2A receptors. However, brexpiprazole displays less intrinsic activity at D 2 receptors and, coupled with actions at 5HT 1A , 5HT 2A and noradrenaline α 1B receptors that are at least as potent as its action at D 2 receptors, is predicted to demonstrate a lower propensity for activating adverse events and extrapyramidal symptoms than aripiprazole. Brexpiprazole 2-4 mg/day produced statistically significant and clinically meaningful improvements in overall symptomatology and psychosocial functioning compared with placebo in adults with acute exacerbation of schizophrenia. As maintenance treatment, brexpiprazole 1-4 mg/day significantly delayed the time to relapse compared with placebo in patients who were already stabilized on the drug and was associated with stabilization or continued improvement in patients' symptoms and functioning. Brexpiprazole was generally well tolerated, exhibiting an adverse event profile characterized by a relatively low incidence of activating and sedating adverse effects, small changes in QT interval and metabolic parameters that were not clinically significant, and moderate weight gain. Clinical evidence to date suggests it usefully extends the range of therapeutic options for schizophrenia.

Aim: This study assessed the long-term safety, tolerability, and maintenance of the therapeutic effect of brexpiprazole in Japanese patients with schizophrenia., Methods: This 52-week, open-label, flexible-dose (1-4 mg/day) study included patients with schizophrenia who continued treatment from a short-term randomized placebo-controlled fixed-dose (1, 2, or 4 mg/day) trial and de novo patients who switched from other antipsychotics., Results: A total of 282 patients (184 de novo and 98 rolled over from short-term trial) entered the 52-week treatment with brexpiprazole, and 150 (53.2%) patients completed the week-52 assessment. Treatment-emergent adverse events (TEAE) were experienced by 235/281 patients (83.6%), and TEAE reported by ≥10% of all patients were nasopharyngitis (23.1%) and worsening of schizophrenia (22.4%). During the study, most of the TEAE were mild or moderate in severity, and there were no deaths, and no clinically meaningful mean changes in laboratory values, vital signs, or electrocardiogram parameters. Mean scores for the Positive and Negative Syndrome Scale total and Clinical Global Impression-Severity remained stable until week 52., Conclusion: Brexpiprazole was generally safe and well tolerated and maintained therapeutic effects in the long-term treatment of Japanese patients with schizophrenia., (© 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.)

The forced oscillation technique (FOT) can measure respiratory mechanics and has attracted attention in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the effects of only indacaterol and tiotropium monotherapies on airflow limitation and respiratory impedance. Pulmonary function tests, COPD assessment test (CAT), and multifrequency FOT with MostGraph-01 were performed at the beginning and after 8 weeks of treatment with indacaterol or tiotropium. The resistance index, resistance at 5 Hz (R5), resistance at 20 Hz (R20), reactance index, reactance at 5 Hz (X5), resonant frequency (Fres), and low-frequency reactance area (ALX) were determined at whole-breath, inspiratory, and expiratory phases. Eighty-two patients (mean age: 73 years; mean forced expiratory volume in 1 second (FEV1): 61.6%±19.0% predicted) were randomized to indacaterol or tiotropium treatment. Both bronchodilators improved airflow limitation, with mean trough improvements in FEV1 of 165 mL and 80 mL in the indacaterol and tiotropium groups, respectively. The CAT score decreased in the indacaterol group (P<0.001; 11.2±6.6 to 7.5±5.6). Compared with tiotropium, indacaterol significantly improved FEV1, percent predicted FEV1, and CAT score (P=0.042, P=0.008, and P=0.027, respectively). For respiratory impedance, indacaterol and tiotropium changed R5, X5, Fres, and ALX at whole-breath, inspiratory, and expiratory phases. In the indacaterol group, the changes in R5, R5-R20, X5, Fres, and ALX were significantly correlated with the changes in FEV1. The use of the FOT may enable the evaluation of the effects of bronchodilators in addition to FEV1-indicated therapeutic effects in COPD.

This randomized, two-way crossover study evaluated the bioavailability of elvitegravir administered as the new individual tablet containing 150 mg and a cobicistat 150 mg tablet, concomitantly with a fixed-dose combination tablet containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (EVG + COBI + FTC/TDF), in comparison with a single-tablet regimen containing the same dose of each component (EVG/COBI/FTC/TDF). Twenty-four healthy Japanese male subjects received the two different elvitegravir treatments, the separate-tablet or single-tablet regimen, once-daily for 10 days in each. The pharmacokinetic parameters (Cmax , AUCtau , and Ctau ) of elvitegravir were investigated at Day 10 after each treatment, together with safety and tolerability. Relative to EVG/COBI/FTC/TDF, the geometric least-squares mean ratios (GMR) and 90% confidence intervals (CIs) for elvitegravir Cmax and AUCtau were within the boundary of 0.8-1.25, while the upper limit of the 90% CI of GMR for Ctau was narrowly below the lack of bioequivalence boundary (0.79). No deaths, serious AEs, or drug-related AEs occurred. In conclusion, Cmax and AUCtau of elvitegravir met the strict definition of bioequivalence, indicating that the two regimens were essentially bioequivalent. Treatment with both regimens for 10 days appeared to be safe and well tolerated., (The Authors. Clinical Pharmacology in Drug Development Published by The American College of Clinical Pharmacology.)

Objectives: This study aimed to evaluate influence of ethnic factors on the pharmacokinetics of orally inhaled QMF149, a novel combination of an approved longacting β2-agonist, indacaterol (Onbrez® Breezhaler® for COPD), and an approved inhaled corticosteroid, mometasone furoate (MF), (Asmanex® Twisthaler® for asthma), following multiple dose administration of QMF149 (indacaterol acetate/MF) 150/80 μg and 150/320 μg via the Breezhaler® device in healthy Japanese and Caucasian subjects., Methods: This was a single-center, openlabel, multiple-dose, two-period, complete crossover study that randomized healthy Japanese and, age and weight matched Caucasian subjects to QMF149 150/80 μg or 150/320 μg once daily (o.d.) for 14 days in each period. Pharmacokinetics (PK) were assessed up to 24 hours on days 1 and 14., Results: 24 Japanese and 24 Caucasian healthy subjects were enrolled. Indacaterol and MF had similar PK profiles across both the doses and both ethnic groups. The maximum geometric mean ratios (90% confidence interval (CI)) for Japanese vs. Caucasian subjects for Cmax were 1.23 (1.11 - 1.38) and 1.24 (1.11 - 1.38) for indacaterol and MF, respectively. For AUC, the maximum ratios were 1.22 (1.09 - 1.36) and 1.30 (1.18 - 1.44) for indacaterol and MF, respectively. The mild trend towards higher exposure in Japanese subjects could be explained by the fact that the mean body weight was 14% higher for Caucasians compared to their Japanese counterparts. No serious adverse events or discontinuations related to study medication were reported., Conclusion: The study demonstrated increase of mean exposure parameters in Japanese subjects vs. Caucasian subjects, which ranged between 19 - 23% and 17 - 30%, for indacaterol and MF components, respectively. Multiple doses of both the QMF149 dose levels were safe and well-tolerated in all subjects. Body weight was considered a key contributory factor for the observed difference in exposure. These results suggest no dose adjustment for QMF149 is required in Asian populations.

Once-daily dual-bronchodilator therapy with combined indacaterol and glycopyrronium bromide in one device (Ultibro, Breezhaler), often called QVA149, was first approved in 2013 in Japan and Europe. As of November 2014, more than 40 countries had approved this medication except for the USA. This is the first dual bronchodilator in one device. Now, the Breezhaler is the only device that can provide long-acting muscarinic antagonist (glycopyrronium bromide), long-acting beta agonist (indacaterol), and a combination of the two medications (QVA149). The choice among the three medications allows a patient to use the same inhalation device even when the regimen is changed from single-bronchodilator therapy to dual-bronchodilator therapy. In addition, the quick bronchodilation effect and once-daily administration can improve patient adherence to medical treatment for chronic obstructive pulmonary disease (COPD). To our knowledge, as of November 2014, the safety and the efficacy of QVA149 have been evaluated in 14 randomized controlled trials. The 14 trials generally showed good safety profiles, and there were better or not-inferior bronchodilator effects of QVA149 when compared with placebo, or other inhaled medication. According to the Japanese Respiratory Society guidelines, QVA149 is a combination of the two first-line bronchodilators. Our meta-analysis indicated that QVA149 is superior to the salmeterol-fluticasone combination to treat COPD in respect of the frequency of adverse effects, exacerbation, pneumonia, and improvement of trough forced expiratory volume in 1 second (FEV1). Thus, we believe that QVA149 can be a key medication for COPD treatments.

Objective: Blonanserin is a novel atypical antipsychotic drug that has efficacy equal to risperidone. We investigated the effects of aripiprazole and blonanserin on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol in the switching strategy of schizophrenia., Methods: Twenty two Japanese patients with schizophrenia were enrolled into this open study. The antipsychotics of all patients were switched to aripiprazole or blonanserin for the improvement of clinical symptoms or side effects. Plasma monoamine metabolites levels were analyzed with high-performance liquid chromatography., Results: There were no significant effects for time (p = 0.346) or time × group interaction (p = 0.27) on the changes of positive and negative syndrome scale (PANSS) total score, although blonanserin decreased PANSS scores. We observed negative correlation between pHVA at baseline and the change in PANSS total score (rs = -0.450, p = 0.046). We also found positive correlation between the changes in pHVA and the changes in PANSS total (rs = 0.536, p = 0.015) and positive (rs = 0.572, p = 0.008) scores., Conclusions: There were no differences between blonanserin and aripiprazole in the improvement of clinical symptoms. Our results suggest that pHVA may be useful indicator for the switching strategy to aripiprazole or blonanserin in schizophrenia., (Copyright © 2014 John Wiley & Sons, Ltd.)

Object: To evaluate the efficacy and safety of aripiprazole and perospirone in Japanese patients with schizophrenia., Methods: In this 12-week, randomized, flexible-dose, open-label study, patients diagnosed with schizophrenia were randomized to receive aripiprazole (3-30 mg/day, n=49) or perospirone (8-48 mg/day, n=51). Efficacy and safety were evaluated using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity Scale (CGI-S), the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and the Barnes Akathisia Rating Scale (BAS) before treatment and every 4 weeks after the initiation of treatment., Results: Fifty-eight patients completed this study (aripiprazole, n=31; perospirone, n=27). No significant differences in gender, episode, age, schizophrenia type, weight, previous treatment and PANSS score were observed between the two groups at baseline. Both groups showed significant improvements during the study, with reductions in the total PANSS scores (Repeated measure analysis of variance, both p<0.0001). There were no significant differences in the PANSS change scores, CGI-S change scores, DIEPSS total score, BAS total score or over time between groups. The most common adverse event was insomnia in both groups., Conclusions: In Japanese schizophrenia patients, aripiprazole and perospirone showed equal efficacy, tolerability and patient compliance. Both drugs showed good efficacy for treating schizophrenia. This paper is the first randomized study to evaluate the comparative efficacy and safety of aripiprazole and perospirone in the treatment of patients with schizophrenia., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aims: The authors investigated the correlation between prolactin concentrations during aripiprazole treatment and various factors, including age, sex, plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, and genetic polymorphisms of dopamine D2 receptor (DRD2) and cytochrome P450(CYP)2D6., Methods: The subjects were 70 inpatients with schizophrenia (36 men and 34 women), receiving fixed doses of aripiprazole (24 mg in 45 cases and 12 mg in 25 cases) for periods of between 2 and 30 weeks. Prolactin concentrations were measured by chemiluminescence immunoassay. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection. The genotypes of Taq1A, -141C Ins/Del DRD2 and CYP2D6 were detected by polymerase chain reaction methods., Results: Prolactin concentrations were significantly higher in women than in men (8.9 ± 7.5 vs 3.4 ± 3.0 ng/mL, P < 0.001). No correlations were found between prolactin concentrations and plasma concentrations of aripiprazole, dehydroaripiprazole or the sum of the two compounds. Prolactin concentrations were not affected by any polymorphism., Conclusion: The present study suggests that only sex plays a significant role in prolactin concentrations during aripiprazole treatment., (© 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.)

Background: The effects of paroxetine coadministration on plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, were studied in 14 Japanese patients with schizophrenia., Methods: The patients had been treated with aripiprazole (24 mg/d in 5 cases, 12 mg/d in 5 cases, and 6 mg/d in 4 cases) for at least 2 weeks. Paroxetine 10 mg/d was coadministered during the first week, and the dose was increased to 20 mg/d during the second week. Blood samples were taken 3 times, before the start of paroxetine and then 1 and 2 weeks after paroxetine coadministration. On the same days, the severity of illness and extrapyramidal adverse effects were evaluated by the clinical global impressions and the Drug-Induced Extra-Pyramidal Symptoms Scale, respectively. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection., Results: Plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole during coadministration of paroxetine 10 and 20 mg/d were significantly (P < 0.05) higher (1.5-fold and 1.7-fold; 1.4-fold and 1.5-fold) than those before paroxetine coadministration. Those values during coadministration of paroxetine 20 mg/d were also significantly (P < 0.05) higher (1.1-fold and 1.1-fold) than those during coadministration of paroxetine 10 mg/d. Plasma concentrations of dehydroaripiprazole were unchanged throughout the study period. The mean clinical global impression score was significantly (P < 0.05) higher during the paroxetine 10 mg/d than that before coadministration, whereas the Drug-Induced Extra-Pyramidal Symptoms Scale scores remained unchanged during the study., Conclusions: This study suggests that lower doses (10-20 mg/d) of paroxetine coadministration increase plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole.

Background: Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD., Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days). Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 microg) or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV(1)AUC(22-24h)) and safety were assessed for 24 h post-dose in each treatment period., Results: Of the 50 patients randomised (92% male; mean age, 67.2 years), 45 completed the study. Standardised FEV(1)AUC(22-24h) was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 microg, respectively (P < 0.001). The improvement in FEV(1) was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points). All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo., Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 microg) provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations.

The purpose of the present study was to evaluate changes in metabolic parameters after switching to aripiprazole in Japanese population. In this 1-year observation study, following a switch to aripiprazole, 32 patients with schizophrenia were observed and assessment was done of bodyweight, total cholesterol, triglyceride, serum prolactin level, and corrected QT (QTc) interval. Significant reductions were observed in these parameters other than QTc interval. Given known detrimental metabolic and hormonal effects of some atypical antipsychotics, a switch to aripiprazole may warrant serious consideration also in Asian patients who suffer those side-effects.

The pharmacokinetics, safety, and pharmacologic effects of OPC-21268, a nonpeptide orally active vasopressin V1 receptor antagonist, have been investigated in 33 healthy subjects. First, 24 subjects were randomly divided into 3 groups of 8, 6 of whom were given 2 ascending single oral doses out of 6 (10, 50, 150, 300, 450, and 600 mg) of OPC-21268 after an overnight fast. The remaining two subjects in each group received placebo as control at each dosing. Additionally, after this procedure, the 6 subjects who received 50-mg single doses were given the same dose in a nonfasting condition. After the single-dose study was completed and the safety and tolerability were ascertained, the remaining 9 subjects, including 3 controls, were given 300 mg of the drug 3 times daily for 7 days (days 3-9) and were given single 100-mg oral doses before (day 1) and after (day 10) this repeated-dose study. OPC-21268 plasma concentrations declined in a monoexponential or biexponential pattern after reaching the maximum plasma concentrations (Cmax). The mean (+/- standard error of the mean) plasma half-life (t1/2) of the alpha phase ranged from 1.31 +/- 0.11 to 1.78 +/- 0.15 hours, and the mean t1/2 of the beta phase ranged from 4.31 +/- 0.28 to 6.28 +/- 0.59 hours. The area under the concentration (AUC0-infinity) and Cmax were proportional to the dose (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)