Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan最新文献_第7页

[Development and Evaluation of At-211 Labeled Peptides]. At-211标记肽的开发与评价

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00146-1

Kazuma Ogawa

引用次数: 0

[The Symposium Organized by Division of Pharmaceutical Health Sciences and Environmental Toxicology: The Impact of Environmental Factors on Maternal and Child Health, and Future Prospects]. [药物健康科学和环境毒理学司举办的专题讨论会：环境因素对妇幼健康的影响及未来展望]。

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00161-F

Kazuma Higashisaka, Tomoki Kimura

引用次数: 0

[Japan's Drug Discovery Capabilities: Current and Future Challenges]. [日本的药物发现能力：当前和未来的挑战]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00167-1

Koji Tawara

引用次数: 0

[Pulmonary Arterial Hypertension Impairs Duodenal Barrier Integrity in Rats]. 肺动脉高压损害大鼠十二指肠屏障完整性。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00165

Shouei Ishimaru, Satoshi Mizuno, Tomoya Tanada, Daisuke Saito, Keiichi Hirono, Keijiro Ibuki, Masato Taguchi

{"title":"[Pulmonary Arterial Hypertension Impairs Duodenal Barrier Integrity in Rats].","authors":"Shouei Ishimaru, Satoshi Mizuno, Tomoya Tanada, Daisuke Saito, Keiichi Hirono, Keijiro Ibuki, Masato Taguchi","doi":"10.1248/yakushi.25-00165","DOIUrl":"10.1248/yakushi.25-00165","url":null,"abstract":"Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that leads to right heart failure and systemic venous congestion. Such congestion can impair multiple organs, including the gastrointestinal tract. Recent clinical studies have reported elevated circulating endotoxin levels in patients with PAH, suggesting a potential disruption of intestinal barrier function. However, whether PAH affects duodenal permeability remains unclear. This study aimed to elucidate the impact of PAH on duodenal barrier integrity. PAH was induced in rats through two subcutaneous injections of monocrotaline (20 mg/kg). Histological analysis was performed, and the mRNA expression levels of duodenal tight junction proteins were quantified using real-time PCR. Duodenal permeability was assessed by performing in situ and ex vivo experiments with paracellular probes. PAH rats exhibited characteristic signs of right heart failure, including reduced weight gain, elevated brain natriuretic peptide levels, and thickening of the right ventricular wall. Histological examination revealed duodenal villous atrophy and thickened muscularis mucosa. Claudin-1 mRNA expression in the duodenum of PAH rats was 70% lower than that in control rats. In situ permeability assays revealed 2.0- and 1.5-fold increases in the portal vein concentrations of polyethylene glycol 400 and 600, respectively. In addition, ex vivo experiments showed a 1.9-fold increase in the cumulative lactulose permeation from the luminal to the vascular side over 120 min. To the best of our knowledge, this is the first report to describe decreased duodenal barrier integrity caused by monocrotaline-induced PAH in rats.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 6","pages":"603-610"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Pharmacokinetics and Metabolic Activations of Drugs in Pharmacology and Toxicology]. [药理学和毒理学中药物的药代动力学和代谢激活]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.26-00112

Hiroshi Yamazaki

{"title":"[Pharmacokinetics and Metabolic Activations of Drugs in Pharmacology and Toxicology].","authors":"Hiroshi Yamazaki","doi":"10.1248/yakushi.26-00112","DOIUrl":"https://doi.org/10.1248/yakushi.26-00112","url":null,"abstract":"The parameters for the absorption, distribution, and metabolic clearance of a wide array of chemicals can be calculated and integrated into a physiologically based pharmacokinetic (PBPK) model that simulates plasma drug concentration over time. Typically, pharmacological and toxicological assessments of chemicals involve estimating human clearance through allometric extrapolation from in vivo rat profiles using empirical compartmental and PBPK models. For patients with genetically impaired cytochrome P450 (P450 or CYP) enzymes who are prescribed only certain drugs, moderate plasma exposure should be noted as a precaution on drug labels, as genetic variants can cause changes in blood concentrations similar to those caused by drug-drug interactions. Many drug oxidations are facilitated by species-specific and polymorphic P450 enzymes and flavin-containing monooxygenases (FMOs). Although interaction study alerts are triggered by a 1.25-fold increase in the clearance of the object drug or the metabolite/parent concentration ratio, such increases may fall within the range of intrinsic baseline variation in vivo of cytochrome CYP3A-dependent phenotypes. The metabolic capacity of polymorphic FMO3 was assessed through urine testing for the levels of food-derived trimethylamine N-oxide. Human PBPK model input parameters for various compounds have been effectively estimated using in silico-generated chemical descriptors and machine learning tools to assess internal exposure in humans without relying on experimental data. This pharmacokinetic modeling approach, which incorporates polymorphic drug-metabolizing enzyme information, can be applied in clinical settings and during computational data-driven evaluations of the potential risks associated with a broad spectrum of chemicals.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 10","pages":"843-864"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[A Case of Suspected Serotonin Syndrome Caused by the Combined Use of Tramadol-acetaminophen Tablets and Fentanyl Patches]. 曲马多-对乙酰氨基酚片与芬太尼贴剂联用致疑似血清素综合征1例

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.26-00001

Maiko Kobayashi, Naoto Hosoi, Naoki Maita, Chisato Ando

{"title":"[A Case of Suspected Serotonin Syndrome Caused by the Combined Use of Tramadol-acetaminophen Tablets and Fentanyl Patches].","authors":"Maiko Kobayashi, Naoto Hosoi, Naoki Maita, Chisato Ando","doi":"10.1248/yakushi.26-00001","DOIUrl":"https://doi.org/10.1248/yakushi.26-00001","url":null,"abstract":"A woman in her 80s was diagnosed with colon cancer, and she underwent chemotherapy after surgery. Oxycodone extended-release tablets were initiated for abdominal pain, but oral administration was difficult, leading to a change to fentanyl patches. Owing to severe numbness from the buttocks to the toes, tramadol/acetaminophen (T/A) tablets were initiated at a dose of 2 tablets per day. The fentanyl patch dose was increased to 2 mg/d, and pain was relieved on combination with 2 T/A tablets. The patient subsequently reported behavioral disturbances, including agitation, anxiety, and sudden diarrhea. She had been taking 1 T/A tablet 2 to 3 times per day at her discretion when the pain worsened. Suspecting an additive effect from the combination of the fentanyl patch and T/A tablets, the T/A tablets were immediately discontinued, and the symptoms resolved. Loxoprofen tablets were initiated at 180 mg/d, and the fentanyl patch dose was increased to 4 mg/d, without side effects such as agitation, anxiety, or behavioral disorders. The combined use of tramadol and fentanyl likely induced excessive serotonergic activity; careful observation is required in adult patients and those receiving multiple medications.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 10","pages":"891-894"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Current Status and Issues of Drug-induced Liver Injury]. [药物性肝损伤的现状及问题]

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00145-F

Atsushi Kawase

引用次数: 0

[Increasing Orphan Drug Loss in Japan: Trends and R&D Strategy for Rare Diseases]. [日益增加的日本孤儿药损失：罕见病的趋势和研发战略]。

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00140-1

Kazuaki Enya

{"title":"[Increasing Orphan Drug Loss in Japan: Trends and R&D Strategy for Rare Diseases].","authors":"Kazuaki Enya","doi":"10.1248/yakushi.25-00140-1","DOIUrl":"https://doi.org/10.1248/yakushi.25-00140-1","url":null,"abstract":"Approximately 7000 rare diseases have been identified globally; however, effective treatments are available for only 5% of them, highlighting substantial unmet medical needs worldwide. In Japan, drug loss-the lack of domestic approval or development of drugs already approved overseas-has become a pressing public health issue. We analyzed orphan drugs (ODs) approved in the United States (U.S.) between 2005 and 2021 to examine trends in OD development in the U.S., drug loss and associated research and development (R&D) models, with the aim of identifying factors that could facilitate more seamless OD development in Japan. Despite a marked increase in OD approvals in the U.S. since 2018, the number of ODs not approved in Japan have increased rapidly, reaching 120 drugs (49%), of which approximately 70% had not entered development, indicating greater OD loss in Japan. U.S./Europe-based startups have become key players in rare disease drug R&D, significantly contributing to this drug loss trend. They successfully develop drugs in the U.S. by combining in-licensing with in-house drug discovery. Out-licensing to Japanese companies or large pharma is critical for expansion into Japan, with successes attributed to drug innovation, target indications, and transactional capabilities. Underlying this trend were Japan's perceived low market potential, its complex clinical trial environment and regulatory requirements, and the financial limitations of startups. These findings highlight the need to foster partnerships with startups and cultivate an ecosystem in Japan that nurtures local startups, to address drug loss and ensure access to promising drugs.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 1","pages":"15-24"},"PeriodicalIF":0.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[How Can We Overcome the Gap in Social Implementation of Medical Technology (Drug & Digital Device Loss) between Japan and Overseas?] 如何克服日本与海外在医疗技术（药品和数字设备丢失）社会实施方面的差距？］

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00140-F

Kota Kodama

引用次数: 0

Incidence and Management of Tirabrutinib-associated Cutaneous Adverse Events: A Case Series. 替拉替尼相关皮肤不良事件的发生率和处理：一个病例系列。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00085

Satoru Matsunuma, Harutaka Seshimo, Shigeki Sunaga, Kunitoshi Otsuka, Toru Koshiishi, Koichi Yoshimoto, Hiroyuki Jimbo

{"title":"Incidence and Management of Tirabrutinib-associated Cutaneous Adverse Events: A Case Series.","authors":"Satoru Matsunuma, Harutaka Seshimo, Shigeki Sunaga, Kunitoshi Otsuka, Toru Koshiishi, Koichi Yoshimoto, Hiroyuki Jimbo","doi":"10.1248/yakushi.25-00085","DOIUrl":"10.1248/yakushi.25-00085","url":null,"abstract":"Cutaneous adverse events associated with tirabrutinib have been reported in clinical trials; however, their overall incidence and severity vary, and real-world data remain limited. This study aimed to assess the incidence and management of tirabrutinib-associated cutaneous adverse events in patients with primary central nervous system lymphoma (PCNSL). This single-center case series included patients with PCNSL who received tirabrutinib treatment between March 1, 2020, and February 29, 2024. Cutaneous adverse events were evaluated using the Common Terminology Criteria for Adverse Events, version 5.0. Patient characteristics, tirabrutinib dosage, concomitant medications, disease severity, time to onset, treatment, and outcomes were analyzed. Seven patients (mean age: 71.1 years, range, 52-88 years) were included herein. Skin disorders were observed in 5 patients (71.4%), including maculopapular rash (grade 2) in 3 patients, erythema multiforme (grade 3) in 1 patient, and eczema-like lesions (grade 2) in 1 patient. The median onset was 22.4 d (range: 1-56 d), with 4 cases occurring within 1 month. Treatments included oral antihistamines (4 cases) and topical corticosteroids (4 cases). One patient discontinued tirabrutinib treatment because of severe cutaneous adverse events. Tirabrutinib-associated cutaneous adverse events were common but manageable, except in 1 case. As most cutaneous adverse events develop within a month, early monitoring is crucial. Large-scale studies are needed to assess the risk factors and preventive strategies for tirabrutinib-associated cutaneous adverse events.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 2","pages":"141-147"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0