記述言語：英語   掲載種別：研究論文（学術雑誌）  

Various types of drugs can affect serum urate levels as side effects. Although these drugs are used to treat different diseases, they might share a structural component that acts on a common target to affect urate levels. Human urate transporter 1 (URAT1) plays an essential role in urate reabsorption at the renal proximal tubule and thus might be a common target for drugs that can affect serum urate levels. Our aim was to elucidate the structural requirements for a compound to show activity toward URAT1 and to identify clinically used drugs that can affect URAT1 activity. Our search was based on structural similarities in the compounds. [14C]Urate uptake by URAT1-expressing human embryonic kidney 293 (HEK-hURAT1) cells in the presence of an analog of a small molecule with known URAT1 activity suggested that structural moieties of salicylic acid can increase URAT1 cis-inhibitory activity. Therefore, we searched a database for drugs with substructures similar to salicylic acid. We were able to predict some types of loop diuretics, statins, and angiotensin receptor blockers as drug candidates that might affect URAT1. In addition, we found that glinides inhibit urate uptake by HEK-hURAT1 cells. Three glinides (nateglinide, mitiglinide, and repaglinide) all inhibited urate uptake by HEK-hURAT1 cells concentration-dependently (IC50: nateglinide, 39 μM; mitiglinide, 63 μM; repaglinide, 3.9 μM). Furthermore, glinides also showed trans-inhibition activity in URAT1-expressing Xenopus oocytes pretreated with the glinides. These findings suggest that glinides sharing a salicylic acid-like substructure might affect serum urate level by acting on URAT1. SIGNIFICANCE STATEMENT: Some types of loop diuretics, statins, angiotensin receptor blockers, and glinides were predicted to affect URAT1, based on their chemical structural similarity to salicylic acid, the structure of which allows it to interact with URAT1. Glinides in particular showed cis- and trans-inhibitory activity toward URAT1.

DOI： 10.1016/j.molpha.2025.100028

PubMed

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The incidence of syphilis is increasing in Japan. A new treatment, penicillin intramuscular injection, was launched in January 2022. This study aimed to determine syphilis treatments in Japan and investigate the impact of the new intramuscular penicillin formulation. MATERIALS AND METHODS: Data from the Japanese Administrative Claims Database from January 2016 to September 2023 were used to identify patients diagnosed with syphilis, and the types and annual trends of antimicrobials prescribed were investigated. Furthermore, the characteristics of patients prescribed an intramuscular injection of benzathine penicillin G were compared with those of patients who were not. RESULTS: Overall, 7867 patients were included in the analysis (81 %, male; 5.4 % positive for human immunodeficiency virus). Seventy-five percent of patients were diagnosed with syphilis in facilities with 0-19 beds. Annual trends showed oral amoxicillin as the most prescribed drug to 80 % of patients throughout the study period. In 2023, 10.6 % of patients received a prescription for an intramuscular penicillin formulation. Compared with those who did not receive this treatment, those who received it tended to have fewer clinic visits over 1 month (p = 0.0256). CONCLUSIONS: Oral amoxicillin is the primary treatment for syphilis in Japan; however, the number of patients receiving intramuscular injection of benzathine penicillin G is increasing. Prescribed mainly by clinics, an intramuscular injection of benzathine penicillin G may contribute to a decreased number of office visits.

DOI： 10.1016/j.jiac.2024.12.015

PubMed

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Trends in opioid use for patients with cancer in Japan remain unclear. This study investigated the prescription trends of strong and weak opioids in Japan and the prescription trends among patients with or without support from a palliative care team. Open data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) and administrative claims data from the University of Yamanashi Hospital from fiscal years 2015 to 2021 were used. Opioid consumption was reported using the defined daily dose (DDD) per 1000 inhabitants per day (DID) and DDD per 100 bed-days. The NDB open data showed a decrease from 0.3111 to 0.2271 in the DID for inpatients (p = 0.0001) and an increase from 0.5971 to 0.8597 in the DID for outpatients (p = 0.0003). Consumption of tramadol, a weak opioid, increased in both inpatient and outpatient settings. In University of Yamanashi Hospital, the annual percentage of opioid consumption changed little among strong opioids (98.1-97.1%) and weak opioids (1.8-2.8%) for patients supported by a palliative care team (p = 0.2842), but changed more noticeably among strong opioids (86.6-69.6%) and weak opioids (13.3-30.3%) for patients without support from a palliative care team (p < 0.001). Opioid prescription patterns in Japan changed during the 7-year study period, which indicated shifts in the types of opioids used. Additionally, the trend in opioid prescriptions was characterized by the presence or absence of palliative care team support.

DOI： 10.1248/bpb.b24-00584

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Background

Neutropenia can easily progress to febrile neutropenia and is a risk factor for life-threatening infections. Predicting and preventing severe neutropenia can help avoid such infections.

Aim

This study aimed to develop an optimal model using advanced statistical methods to predict neutropenia after 5-fluorouracil/cisplatin chemotherapy for esophageal cancer and to create a nomogram for clinical application.

Method

Patients who received 5-fluorouracil/cisplatin chemotherapy at Chiba University Hospital, Japan, between January 2011 and March 2021 were included. Clinical parameters were measured before the first, second, and third chemotherapy cycles and were randomly divided by patient into a training cohort (60%) and test cohort (40%). The predictive performance of Logistic, Stepwise, Lasso, and GLMMLasso models was evaluated by the area under the receiver-operating characteristic curve (AUC). A nomogram based on GLMMLasso was developed, and the accuracy of probabilistic predictions was evaluated by the Brier score.

Results

The AUC for the first cycle of chemotherapy was 0.781 for GLMMLasso, 0.751 for Lasso, 0.697 for Stepwise, and 0.669 for Logistic. The respective AUCs for GLMMLasso in the second and third cycles were 0.704 and 0.900. The variables selected by GLMMLasso were cisplatin dose, 5-fluorouracil dose, use of leucovorin, sex, cholinesterase, and platelets. A nomogram predicting neutropenia was created based on each regression coefficient. The Brier score for the nomogram was 0.139.

Conclusion

We have developed a predictive model with high performance using GLMMLasso. Our nomogram can represent risk visually and may facilitate the assessment of the probability of chemotherapy-induced severe neutropenia in clinical practice.

DOI： 10.1007/s11096-024-01836-5

PubMed

その他リンク： https://link.springer.com/article/10.1007/s11096-024-01836-5/fulltext.html

記述言語：日本語   出版者・発行元：(一社)日本医薬品情報学会  

総ページ数：298   記述言語：日本語   著書種別：教科書・概説・概論

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語