Fundamental & Clinical Pharmacology最新文献

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Discussed poster abstracts—PM2 讨论海报摘要- pm2

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology

Pub Date : 2025-06-23 DOI: 10.1111/fcp.70022

引用次数: 0

Drug news and therapeutic news 药物新闻和治疗新闻

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology

Pub Date : 2025-06-23 DOI: 10.1111/fcp.70017

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Oral communication abstracts 口头交流摘要

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology

Pub Date : 2025-06-23 DOI: 10.1111/fcp.70018

引用次数: 0

Thesis awards 论文奖

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology

Pub Date : 2025-06-23 DOI: 10.1111/fcp.70020

引用次数: 0

Discussed poster abstracts—PM1 讨论海报摘要- pm1

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology

Pub Date : 2025-06-23 DOI: 10.1111/fcp.70021

引用次数: 0

Poster abstracts 海报摘要

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology

Pub Date : 2025-06-23 DOI: 10.1111/fcp.70023

引用次数: 0

Theme and main topic index 主题和主题索引

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology

Pub Date : 2025-06-23 DOI: 10.1111/fcp.70024

引用次数: 0

Risk Factors and Multiple Interaction Effects for Hyperammonemia in Patients Receiving Valproic Acid 丙戊酸治疗患者高氨血症的危险因素及多重相互作用

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology

Pub Date : 2025-06-22 DOI: 10.1111/fcp.70030

Chien-Chou Su, Tsai-Kuei Huang, Ching-Sen Shih, Yi-Chia Su

Background

Valproic acid (VPA) use is associated with an increased risk of hyperammonemia (HA); however, the specific interactions between HA risk factors in VPA-treated patients remain unclear.

Objectives

This study aimed to identify and assess the effects of multiple interactions between different risk factors affecting HA to improve clinical risk stratification in patients undergoing VPA therapy.

Methods

We conducted a retrospective cohort study by reviewing the medical records of patients treated with VPA at a single center from January 2019 to December 2021. The SHapley Additive exPlanations (SHAP) method was used to interpret model predictions, revealing the relative importance and interactions of factors affecting HA risk. SHAP interaction scores were used to assess the effects of multiple interactions between features, providing a comprehensive analysis of how risk factors interact.

Results

This study identified the Top 15 predictors of HA, ranked by importance: patient age, VPA blood concentration, VPA dose, epilepsy, VPA treatment duration, levetiracetam use, hypertension, mental disorders, and number of medications. Notable multiple interaction effects were observed, particularly between age and factors including VPA concentration, epilepsy, and treatment duration. Younger patients and those with elevated VPA concentrations were at increased risk of developing HA, especially when epilepsy or polypharmacy were present.

Conclusions

This study highlights several critical factors potentially influencing HA development in VPA-treated patients, particularly younger patients, those with epilepsy, or those undergoing polypharmacy. However, as a single-center retrospective study, these findings necessitate further validation through additional research.

背景丙戊酸（VPA）的使用与高氨血症（HA）的风险增加有关；然而，在vpa治疗的患者中，HA危险因素之间的具体相互作用尚不清楚。本研究旨在识别和评估影响HA的不同危险因素之间多重相互作用的影响，以改善VPA治疗患者的临床风险分层。方法通过回顾2019年1月至2021年12月在单一中心接受VPA治疗的患者的病历，进行回顾性队列研究。使用SHapley加性解释（SHAP）方法解释模型预测，揭示影响HA风险的因素的相对重要性和相互作用。SHAP相互作用评分用于评估特征之间多重相互作用的影响，提供了对危险因素如何相互作用的全面分析。结果本研究确定了HA的前15个预测因素，按重要性排序：患者年龄、VPA血药浓度、VPA剂量、癫痫、VPA治疗时间、左乙西坦使用、高血压、精神障碍和药物数量。观察到明显的多重相互作用效应，特别是年龄与VPA浓度、癫痫和治疗时间等因素之间的相互作用。年轻患者和VPA浓度升高的患者发生HA的风险增加，特别是当癫痫或多药并存时。本研究强调了几个可能影响vpa治疗患者HA发展的关键因素，特别是年轻患者、癫痫患者或接受多种药物治疗的患者。然而，作为一项单中心回顾性研究，这些发现需要通过额外的研究进一步验证。

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引用次数: 0

Fluvoxamine Attenuates Liver Injury in Lipopolysaccharide-Induced Sepsis: Via Nrf2/HO-1 Pathway 氟伏沙明通过Nrf2/HO-1途径减轻脂多糖诱导脓毒症的肝损伤

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology

Pub Date : 2025-06-20 DOI: 10.1111/fcp.70031

Rahime Aslankoc, Ozlem Ozmen, Pınar Karabacak, Cahide Aslan, Oguzhan Kavrik, Okan Sancer

The search for new treatments for sepsis is a pivotal subject of survey owing to the high mortality of sepsis. Sepsis can cause serious injury to many vital organs, including the liver. This study investigated the potential therapeutic impacts of fluvoxamine (FLV) against liver injury in a lipopolysaccharide (LPS)-induced sepsis model. Thirty-two female Wistar Albino rats were divided into four equal groups: control, LPS (5 mg/kg, i.p., single dose), LPS + FLV(5 mg/kg, i.p., single dose+50 mg/kg, i.p., single dose, 30 min before LPS application) and FLV(50 mg/kg, i.p., single dose). Six hours after LPS application, blood and liver tissues were gathered under anesthesia for biochemical, histopathological, and immunohistochemical analyses. The RT-qPCR analyzed the mRNA expression of nuclear factor erythroid 2–related factor 2 (Nrf2), glycogen synthase kinase-3 (GSK3ß), kelch-like ECH–associated protein 1 (Keap1), and heme oxygenase-1 (HO-1). LPS administration caused significant histopathological changes in the liver and increased oxidative stress. It increased the number of TNF-α, osteopontin (OPN), and serum amyloid A (SAA) immune positive cells associated with inflammation and decreased Nrf2, GSK3ß, Keap1, and HO-1 gene expressions associated with antioxidant defense. Additionally, serum alanine aminotransferase (ALT) level significantly increased. In the LPS + FLV and FLV groups, improvement in histopathological findings and a significant decrease in oxidative stress were detected. TNF-α, OPN, and SAA expression decreased, and Nrf2, GSK3ß, Keap1, and HO-1 gene expressions increased. The decrease in serum aspartate aminotransferase (AST) and ALT was found to be significant only in the FLV group. Our findings therefore provide new evidence that FLV reduces LPS-induced liver injury.

由于脓毒症的高死亡率，寻找新的脓毒症治疗方法是一个关键的调查主题。败血症会对包括肝脏在内的许多重要器官造成严重伤害。本研究在脂多糖（LPS）诱导的脓毒症模型中探讨氟伏沙明（FLV）对肝损伤的潜在治疗作用。将32只雌性Wistar Albino大鼠分为4组：对照组、LPS （5 mg/kg， 1次注射，单剂量）、LPS + FLV（5 mg/kg， 1次注射，单剂量）+50 mg/kg， 1次注射，单剂量，LPS应用前30 min)和FLV（50 mg/kg， 1次注射，单剂量）。LPS应用6小时后，麻醉下采集血液和肝脏组织进行生化、组织病理学和免疫组织化学分析。RT-qPCR分析核因子红系2相关因子2 （Nrf2）、糖原合成酶激酶3 （GSK3ß）、kelch样ech相关蛋白1 （Keap1）、血红素加氧酶1 (HO-1) mRNA表达情况。LPS处理引起肝脏明显的组织病理学改变和氧化应激增加。它增加了与炎症相关的TNF-α、骨桥蛋白（OPN）和血清淀粉样蛋白A （SAA）免疫阳性细胞的数量，降低了与抗氧化防御相关的Nrf2、GSK3ß、Keap1和HO-1基因的表达。血清谷丙转氨酶（ALT）水平显著升高。在LPS + FLV组和FLV组中，检测到组织病理学结果的改善和氧化应激的显著降低。TNF-α、OPN、SAA表达降低，Nrf2、GSK3ß、Keap1、HO-1基因表达升高。血清谷草转氨酶（AST）和谷丙转氨酶（ALT）仅在FLV组显著降低。因此，我们的研究结果提供了新的证据，证明FLV可以减少lps诱导的肝损伤。

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引用次数: 0

Cannabinoids and Adverse Convulsive Effects: A Pharmacovigilance and Addictovigilance Analysis of Cases Reported in France 大麻素和不良惊厥效应：法国报告的病例的药物警戒和成瘾警戒分析

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology

Pub Date : 2025-06-20 DOI: 10.1111/fcp.70028

Marie-Laure Laroche, Marion Labetoulle, Emilie Jouanjus, Edeltraut Kröger, Arsène Zongo

Background

Seizures after the use of cannabinoids are reported, but no precise descriptions of the characteristics of subjects and factors that may trigger seizures are available.

Objectives

To study the characteristics and circumstances associated with the occurrence of seizures in individuals using cannabinoids for medical or recreational purposes.

Methods

A retrospective analysis of spontaneous reports of adverse drug effects issued by the French pharmacovigilance and addictovigilance systems, and by manufacturers, extracted data from the Eudravigilance database (01/01/1985–21/07/2023). The request used the broad MedDRA SMQ term ‘convulsive’, with all products containing cannabinoids (THC, CBD, cannabis or natural cannabinoids).

Results

Among 4296 notifications with cannabinoids, 130 (3%) reports of convulsive effects were analysed: 29 cases (23.3%) related to medical use (27 CBD, 1 THC and 2 combined THC/CBD preparations) and 98 (75.4%) related to recreational use. The median age was 29.0 years (min-max: 3–75), 78.7% were men and 81.1% were serious cases. Among the recreational users, 38.8% used Cannabis sativa with a history of epilepsy, and 68.4% of them were taking antiepileptics. In total, 67.7% of individuals had at least one risk factor for seizures, i.e., 31.0% among medical users and 78.6% among recreational users. The main risk factors with medical use were inefficacy of CBD (17.2%), fatigue (13.8%) and concomitant epileptogenic medications (10.3%). The main risk with recreational use was concomitant epileptogenic medications (39.8%), consumption of illicit drugs (33.7%) and alcohol (32.7%).

Conclusion

This analysis demonstrates the importance of alerting cannabinoid users, particularly recreational cannabis users and those with a history of epilepsy, about seizure-associated risks. Moreover, educational information should be provided together with the prescription of licensed cannabinoids and medical cannabis.

背景：使用大麻素后癫痫发作的报道，但没有准确的描述对象的特征和可能引发癫痫发作的因素。目的研究以医疗或娱乐为目的使用大麻素的个体癫痫发作的特征和相关情况。方法从Eudravigilance数据库（1985年1月1日- 2023年7月21日）中提取数据，对法国药物警戒系统和成瘾警戒系统以及生产商发布的药物不良反应自发报告进行回顾性分析。该请求使用了广义的MedDRA SMQ术语“惊厥”，所有产品都含有大麻素（四氢大麻酚、CBD、大麻或天然大麻素）。结果在4296例大麻素通报中，分析了130例（3%）惊厥效应报告：29例（23.3%）与医疗用途（27例CBD、1例THC和2例THC/CBD联合制剂）有关，98例（75.4%）与娱乐用途有关。中位年龄29.0岁（最小-最大3-75岁），男性占78.7%，重症占81.1%。在娱乐性大麻使用者中，38.8%的人有癫痫史，68.4%的人服用抗癫痫药物。总的来说，67.7%的人至少有一种癫痫发作的危险因素，即，31.0%的医疗使用者和78.6%的娱乐使用者。医疗使用的主要危险因素是CBD无效（17.2%）、疲劳（13.8%）和伴随的致癫痫药物（10.3%）。娱乐性用药的主要风险是同时服用致癫痫药物（39.8%）、非法药物（33.7%）和酒精（32.7%）。结论：该分析表明，提醒大麻素使用者，特别是娱乐性大麻使用者和有癫痫史的人有关癫痫相关风险的重要性。此外，应在提供有执照的大麻素和医用大麻处方的同时提供教育信息。

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