Search

Rapid Asian economic development might engender secondary impacts of atmospheric aerosol particles over the western Pacific after conversion of gaseous pollutants such as SO2. To elucidate changes in aerosol concentrations in leeward areas undergoing remarkable industrialization, the number-size distributions of submicrometer (0.3-1.0 μm) aerosols were measured at Murododaira (36.6° N, 137.6° E, 2450ma.s.l.) on the western flank of Mount Tateyama in central Japan during January 1999-February 2009. Nighttime data obtained from 2400 to 0500 were used to analyze free-tropospheric aerosol concentration. Monthly average volume concentrations were calculated for months with >50% daily data coverage. Volume concentrations of submicrometer aerosols were high in spring to early summer and low in winter. Significant increasing trends at 95% confidence levels were found for volume concentrations in winter-spring. Simulated monthly anthropogenic aerosol concentrations at Mt. Tateyama from results of regional aerosol modeling with emission inventory up to 2005 showed seasonal variation and winter-spring increasing trends similar to those of observed aerosol concentration. According to the model analyses, the contribution of anthropogenic aerosol concentrations derived from China was high during winter-spring (60-80% of total anthropogenic aerosols at Mt. Tateyama). This accords with the increasing trend observed for winter-spring. Because SO2- 4, in China, engender enhancement of submicrometerdiameter aerosols over Japan during winter-spring. [ABSTRACT FROM AUTHOR]2, in China, engender enhancement of submicrometerdiameter aerosols over Japan during winter-spring. [ABSTRACT FROM AUTHOR]

Quizartinib is a potent, oral, second-generation, selective type II FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor. It has shown improved overall survival in a randomized, multinational, Phase 3 (QuANTUM-First) study in patients with FLT3-internal tandem duplication (ITD)-positive newly diagnosed acute myeloid leukemia. We conducted 2 Phase 1b studies in Japan and China to evaluate the safety, pharmacokinetics, and efficacy of quizartinib in combination with standard induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia. Quizartinib was started at a dose level of 20 mg/day and then escalated to 40 mg/day, the dose used in the Phase 3 study. Seven patients were enrolled according to the 3 + 3 dose-escalation method in each study, including 3 patients who were FLT3-ITD positive. No dose-limiting toxicities were observed at dose levels up to 40 mg/day in both studies. Grade 3 or higher, quizartinib-related, treatment-emergent adverse events included febrile neutropenia, hematologic toxicities, and infections. QT prolongation on electrocardiogram was observed in 5 patients. The pharmacokinetics of quizartinib and its metabolite AC886 were similar between the studies and consistent with previous findings in the United States. We confirmed the tolerability of Japanese and Chinese patients to the dose of quizartinib and chemotherapy regimens used in the QuANTUM-First study., (© 2024 Daiichi Sankyo Co., Ltd. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)