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Messenger interference RNA therapies targeting apolipoprotein C-III and angiopoietin-like protein 3 for mixed hyperlipidemia: the future of plozasiran and zodasiran. 针对脂蛋白 C-III 和血管生成素样蛋白 3 的信使干扰 RNA疗法治疗混合型高脂血症:plozasiran 和 zodasiran 的未来。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-29 DOI: 10.1080/17512433.2024.2423724
Zonghao Pan, Muhammad Adnan Zaman, Sidra Kalsoom, Yani Zhang

Introduction: Mixed hyperlipidemia represents a substantial public health issue, and a considerable burden on healthcare systems. Although the introduction of statins and LDL-cholesterol lowering agents have significantly reduced the incidence of atherosclerotic cardiovascular diseases (ASCVD), a significant portion of the population continues to exhibit ASCVD progression due to elevated triglyceride-rich lipoproteins (TRLs) levels. This persistent risk has catalyzed the development of novel pharmacological interventions targeting these lipoproteins.

Areas covered: Our special report commenced with a targeted PubMed search using keywords such as 'plozasiran,' 'zodasiran,' and terms related to APOC3 and ANGPTL3. As the review progressed, emergent research questions guided further searches, allowing for the inclusion of additional relevant articles to comprehensively illustrate the linkage between TRLs and cardiovascular disease, discuss the roles of APOC3, ANGPTL3, and the pharmaceutical agents that target these proteins, and provide a comparison on the ARCHES-2 and MUIR trials.

Expert opinion: The ARCHES-2 and MUIR trials demonstrated effective triglyceride reduction by these therapies, yet it is uncertain if this correlates with significant clinical benefits. Advances in antisense oligonucleotide technology, especially the GalNAc delivery platform, show promise for personalized lipid management, though challenges such as cost and safety concerns remain.

导言:混合型高脂血症是一个重大的公共卫生问题,也是医疗系统的沉重负担。尽管他汀类药物和降低低密度脂蛋白胆固醇药物的引入大大降低了动脉粥样硬化性心血管疾病(ASCVD)的发病率,但由于富含甘油三酯的脂蛋白(TRLs)水平升高,仍有相当一部分人群的 ASCVD 病情持续恶化。这种持续存在的风险促进了针对这些脂蛋白的新型药物干预措施的开发:我们的特别报告首先使用 "plozasiran"、"zodasiran "等关键词以及与 APOC3 和 ANGPTL3 相关的术语在 PubMed 上进行了有针对性的搜索。随着综述的深入,新出现的研究问题引导了进一步的搜索,从而纳入了更多的相关文章,以全面说明TRL与心血管疾病之间的联系,讨论APOC3、ANGPTL3和针对这些蛋白的药物的作用,并对ARCHES-2和MUIR试验进行比较:ARCHES-2和MUIR试验表明,这些疗法能有效降低甘油三酯,但还不能确定这是否与显著的临床疗效相关。反义寡核苷酸技术的进步,尤其是 GalNAc 递送平台,为个性化血脂管理带来了希望,但成本和安全性等挑战依然存在。
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引用次数: 0
SGLT2i and GLP1RA effects in patients followed in a hospital diabetology consultation. SGLT2i 和 GLP1RA 对医院糖尿病咨询随访患者的影响。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-27 DOI: 10.1080/17512433.2024.2421872
António Cabral Lopes, Olga Lourenço, Manuel Morgado

Background: We aimed to investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) in patients with type 2 diabetes mellitus (T2DM) in clinical practice.

Research design and methods: A total of 340 patients were included. Data on age, gender, antidiabetic medications, and bioanalytical parameters were collected at baseline and one year later. Were analyzed estimated glomerular filtration rate (eGFR), blood sodium and potassium levels, blood pressure, weight, cardiovascular risk, and glycated hemoglobin (HbA1c).

Results: Patients treated with SGLT2i exhibited a significant improvement in eGFR at the endpoint compared to baseline (p = 0.006). Both treatment groups experienced reductions in systolic blood pressure at the endpoint; especially patients treated with SGLT2i (p = 0.0002). GLP1RA treatment resulted in a statistically significant weight reduction from baseline to endpoint (p < 0.0001), with a higher percentage of patients achieving ≥ 5% weight loss compared to the non-GLP1RA group (33.6% vs. 19.8%). Both SGLT2i and GLP1RA treatments significantly reduced cardiovascular risk scores (p = 0.004 and p = 0.002, respectively). Additionally, both treatments were associated with a significant reduction in HbA1c levels at the endpoint (p = 0.010 and p = 0.002, respectively).

Conclusions: Our findings suggest that SGLT2i and GLP1RA offer beneficial effects in patients with T2DM.

背景:我们旨在研究钠-葡萄糖共转运体 2 抑制剂(SGLT2i)和胰高血糖素样肽-1 受体激动剂(GLP1RA)在临床实践中对 2 型糖尿病(T2DM)患者的影响:共纳入 340 例患者。研究设计和方法:共纳入 340 名患者,收集基线和一年后的年龄、性别、抗糖尿病药物和生物分析参数数据。对估计肾小球滤过率(eGFR)、血钠和血钾水平、血压、体重、心血管风险和糖化血红蛋白(HbA1c)进行了分析:结果:接受 SGLT2i 治疗的患者在终点时的 eGFR 与基线相比有显著改善(p = 0.006)。两个治疗组在终点时收缩压都有所下降,尤其是接受 SGLT2i 治疗的患者(p = 0.0002)。GLP1RA 治疗使患者体重从基线到终点均有显著下降(分别为 p = 0.004 和 p = 0.002)。此外,两种治疗方法在终点都能显著降低 HbA1c 水平(分别为 p = 0.010 和 p = 0.002):我们的研究结果表明,SGLT2i 和 GLP1RA 可为 T2DM 患者带来益处。
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引用次数: 0
Renin-angiotensin system inhibition and mortality in patients undergoing dialysis with coronary artery disease: insights from a multi-center observational study. 肾素-血管紧张素系统抑制与冠心病透析患者的死亡率:一项多中心观察研究的启示。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-23 DOI: 10.1080/17512433.2024.2419915
Enmin Xie, Shuoyan An, Yaxin Wu, Zixiang Ye, Xuecheng Zhao, Yike Li, Nan Shen, Yanxiang Gao, Jingang Zheng

Background: While the survival benefits of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are firmly established in the general population, their efficacy within patient undergoing dialysis with coronary artery disease (CAD) remains controversial.

Methods: Between January 2015 and June 2021, 1168 patients undergoing dialysis with CAD were assessed from 30 tertiary medical centers. The primary outcome was all-cause death, and the secondary outcome was cardiovascular death. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for between-group differences.

Results: Overall, ACEI or ARB were prescribed to 518 patients (44.3%) upon discharge. After a median follow-up of 22.2 months, 361 (30.9%) patients died, including 243 cardiovascular deaths. The use of ACEI or ARB was associated with a significantly lower risk of all-cause (25.3% vs 35.4%, hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52-0.82, p < 0.001) and cardiovascular death (17.0% vs 23.8%; HR 0.64, 95% CI 0.48-0.83, p = 0.001). These findings remained consistent across IPTW and PSM analyses. Sensitivity analyses for ACEI and ARB use separately yielded similar results.

Conclusions: Our findings suggested that among patients undergoing dialysis with CAD, ACEI or ARB use was associated with a lower risk of all-cause and cardiovascular death.

背景:虽然血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体阻滞剂(ARB)对普通人群的生存益处已得到证实,但它们对接受透析的冠状动脉疾病(CAD)患者的疗效仍存在争议:2015年1月至2021年6月期间,30家三级医疗中心对1168名接受透析治疗的冠心病患者进行了评估。主要结果为全因死亡,次要结果为心血管死亡。为考虑组间差异,进行了逆概率治疗加权(IPTW)和倾向评分匹配(PSM):共有 518 名患者(44.3%)在出院时接受了 ACEI 或 ARB 治疗。中位随访 22.2 个月后,361 名患者(30.9%)死亡,其中 243 人死于心血管疾病。使用 ACEI 或 ARB 可显著降低全因风险(25.3% vs 35.4%,危险比 [HR] 0.65,95% 置信区间 [CI] 0.52-0.82,P = 0.001)。这些结果在IPTW和PSM分析中保持一致。对分别使用 ACEI 和 ARB 的敏感性分析也得出了相似的结果:我们的研究结果表明,在患有 CAD 的透析患者中,使用 ACEI 或 ARB 与较低的全因死亡和心血管死亡风险相关。
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引用次数: 0
Semaglutide and smoking cessation in individuals with type 2 diabetes mellitus: there is no smoke without fire! 塞马鲁肽与 2 型糖尿病患者的戒烟:无烟不成火!
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-21 DOI: 10.1080/17512433.2024.2418398
Djordje S Popovic, Dimitrios Patoulias, Theocharis Koufakis, Paschalis Karakasis, Ieva Ruža, Nikolaos Papanas

Tobacco use represents the leading preventable risk factor for premature deaths worldwide. A meta-analysis of 74 epidemiological studies, including 3.2 million individuals with type 2 diabetes mellitus (T2DM) from 33 countries, reported a pooled prevalence of smoking of 20.8% among individuals with T2DM. Cigarette smoking further aggravates existing deleterious vascular effects of T2DM. Namely, chronic hyperglycemia and exposure to cigarette smoke cause additive injurious effect on the endothelium, leading to an acceleration of vascular complications seen in persons with T2DM and tobacco use disorders (TUD). In a recent study, Wang and colleagues found that semaglutide use was associated with a significantly lower risk for medical encounters for TUD, when compared to other antidiabetic drug classes; indeed, this effect was strongest compared with insulins and weakest compared with other glucagon-like peptide-1 receptor agonists. Semaglutide was associated with reduced smoking cessation medication prescriptions and counseling. Similar findings were observed irrespective of the presence of obesity. Therefore, semaglutide use might be useful in terms of smoking cessation among individuals with T2DM, thus offering an additional benefit for this constantly growing population. However, those interesting findings should be confirmed through dedicated, large-scale randomized controlled trials.

吸烟是导致全球过早死亡的主要可预防风险因素。一项对 74 项流行病学研究(包括来自 33 个国家的 320 万 2 型糖尿病(T2DM)患者)的荟萃分析报告显示,T2DM 患者的吸烟率为 20.8%。吸烟进一步加剧了 T2DM 对血管的有害影响。也就是说,慢性高血糖和暴露于香烟烟雾会对血管内皮产生叠加伤害效应,从而加速 T2DM 和烟草使用障碍(TUD)患者的血管并发症。在最近的一项研究中,Wang 及其同事发现,与其他抗糖尿病药物相比,使用塞马鲁肽可显著降低因 TUD 而就医的风险;事实上,与胰岛素相比,这种效应最强,而与其他胰高血糖素样肽-1 受体激动剂相比,这种效应最弱。塞马鲁肽与戒烟药物处方和咨询的减少有关。无论是否存在肥胖,都观察到了类似的结果。因此,使用塞马鲁肽可能有助于T2DM患者戒烟,从而为这一不断增长的人群带来额外的益处。不过,这些有趣的发现还需要通过专门的大规模随机对照试验来证实。
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引用次数: 0
Type II RAF inhibitor tovorafenib for the treatment of pediatric low-grade glioma. 治疗小儿低级别胶质瘤的 II 型 RAF 抑制剂托伐非尼。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-19 DOI: 10.1080/17512433.2024.2418405
Tianqiao Zhang, Bo Xu, Fan Tang, Zunbo He, Jiecan Zhou

Introduction: Pediatric low-grade glioma (pLGG) is the most prevalent childhood brain tumor group, currently regarded as a chronic disease. On 23 April 2024, the U.S. FDA approved a new type II RAF inhibitor, tovorafenib (OJEMDATM), previously known as DAY101, for the treatment of patients aged 6 months and older with relapsed or refractory (R/R) pLGG harboring a BRAF fusion or rearrangement, or BRAF V600E mutation.

Areas covered: This article aims to review the pharmacological properties of tovorafenib and evaluate its efficacy and safety in the treatment of R/R pLGG. We conducted a systematic search of PubMed and Web of Science databases for English-language publications related to tovorafenib, including journal articles and conference abstracts, up through 20 August 2024.

Expert opinion: As the first and only FDA-approved medicine for children with BRAF fusions or rearrangements, which are the most common molecular alteration in pLGG, tovorafenib shows superior central nervous system penetration without the paradoxical activation of the MAPK pathway reported for type I BRAF inhibitors. Phase 1 and the pivotal phase 2 trials have demonstrated that tovorafenib monotherapy is generally well-tolerated and exhibits encouraging signs of meaningful, rapid and sustained clinical activity in children and young adults with BRAF-altered pLGG.

简介小儿低级别胶质瘤(pLGG)是发病率最高的儿童脑肿瘤,目前被视为一种慢性疾病。2024 年 4 月 23 日,美国 FDA 批准了一种新型 II 型 RAF 抑制剂--托伐非尼(OJEMDATM)(之前名为 DAY101),用于治疗年龄在 6 个月及以上、携带 BRAF 融合或重排或 BRAF V600E 突变的复发或难治性(R/R)pLGG 患者:本文旨在回顾托伐非尼的药理特性,并评估其治疗R/R pLGG的有效性和安全性。我们在PubMed和Web of Science数据库中系统检索了截至2024年8月20日与沃拉非尼相关的英文出版物,包括期刊论文和会议摘要:作为首个也是唯一一个获得FDA批准的治疗儿童BRAF融合或重排(pLGG中最常见的分子改变)的药物,tovorafenib显示出卓越的中枢神经系统穿透力,而不会出现I型BRAF抑制剂所报道的MAPK通路激活的矛盾现象。1 期和关键的 2 期试验表明,托伐非尼单药治疗的耐受性普遍良好,而且在患有 BRAF 改变的 pLGG 的儿童和年轻成人中显示出令人鼓舞的有意义、快速和持续的临床活性。
{"title":"Type II RAF inhibitor tovorafenib for the treatment of pediatric low-grade glioma.","authors":"Tianqiao Zhang, Bo Xu, Fan Tang, Zunbo He, Jiecan Zhou","doi":"10.1080/17512433.2024.2418405","DOIUrl":"https://doi.org/10.1080/17512433.2024.2418405","url":null,"abstract":"<p><strong>Introduction: </strong>Pediatric low-grade glioma (pLGG) is the most prevalent childhood brain tumor group, currently regarded as a chronic disease. On 23 April 2024, the U.S. FDA approved a new type II RAF inhibitor, tovorafenib (OJEMDA<sup>TM</sup>), previously known as DAY101, for the treatment of patients aged 6 months and older with relapsed or refractory (R/R) pLGG harboring a BRAF fusion or rearrangement, or BRAF V600E mutation.</p><p><strong>Areas covered: </strong>This article aims to review the pharmacological properties of tovorafenib and evaluate its efficacy and safety in the treatment of R/R pLGG. We conducted a systematic search of PubMed and Web of Science databases for English-language publications related to tovorafenib, including journal articles and conference abstracts, up through 20 August 2024.</p><p><strong>Expert opinion: </strong>As the first and only FDA-approved medicine for children with BRAF fusions or rearrangements, which are the most common molecular alteration in pLGG, tovorafenib shows superior central nervous system penetration without the paradoxical activation of the MAPK pathway reported for type I BRAF inhibitors. Phase 1 and the pivotal phase 2 trials have demonstrated that tovorafenib monotherapy is generally well-tolerated and exhibits encouraging signs of meaningful, rapid and sustained clinical activity in children and young adults with BRAF-altered pLGG.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Understanding the efficacy and tolerability of migraine treatment: a deep dive into CGRP antagonists. 了解偏头痛治疗的疗效和耐受性:深入研究 CGRP 拮抗剂。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-18 DOI: 10.1080/17512433.2024.2417655
Marta Waliszewska-Prosół, Bianca Raffaelli, Marcin Straburzyński, Paolo Martelletti

Introduction: The discovery of the role of the calcitonin gene-related peptide (CGPR) in migraine pathogenesis ushered in a new era in headache medicine. This evidence led to the development of small-molecule CGRP receptor antagonists and monoclonal antibodies targeting either CGRP or its receptor.

Areas covered: We will present selected aspects of the role of CGRP in the pathogenesis of migraine, the efficacy of CGRP-targeted treatment, and the still-open questions regarding the practical application of CGRP antagonists in headache medicine.

Expert opinion: CGRP-targeting drugs represent a transformative approach to migraine treatment, offering superior efficacy and tolerability compared to traditional therapies, they are a helpful addition to the treatment arsenal but also have their flaws and require further observation. Their availability provides new hope for migraine patients, particularly those who have not responded adequately to conventional treatments. Future directions for migraine care planning, especially for chronic migraine and medication-overuse headache, should include universal access to these specific and effective forms of therapy to prevent complications from the disease and its negative effects in many aspects of a patient's life.

导言:降钙素基因相关肽(CGPR)在偏头痛发病机制中的作用的发现,开创了头痛医学的新纪元。这一证据推动了小分子 CGRP 受体拮抗剂和针对 CGRP 或其受体的单克隆抗体的开发:我们将从 CGRP 在偏头痛发病机制中的作用、CGRP 靶向治疗的疗效以及 CGRP 拮抗剂在头痛医学中的实际应用等方面进行介绍:CGRP靶向药物代表了偏头痛治疗的一种变革性方法,与传统疗法相比,其疗效和耐受性更胜一筹,是治疗手段的有益补充,但也存在缺陷,需要进一步观察。它们的出现为偏头痛患者,尤其是对传统疗法反应不佳的患者带来了新的希望。偏头痛治疗规划的未来方向,尤其是针对慢性偏头痛和药物滥用性头痛的治疗规划,应包括普及这些特殊而有效的治疗方法,以预防疾病的并发症及其对患者生活诸多方面的负面影响。
{"title":"Understanding the efficacy and tolerability of migraine treatment: a deep dive into CGRP antagonists.","authors":"Marta Waliszewska-Prosół, Bianca Raffaelli, Marcin Straburzyński, Paolo Martelletti","doi":"10.1080/17512433.2024.2417655","DOIUrl":"https://doi.org/10.1080/17512433.2024.2417655","url":null,"abstract":"<p><strong>Introduction: </strong>The discovery of the role of the calcitonin gene-related peptide (CGPR) in migraine pathogenesis ushered in a new era in headache medicine. This evidence led to the development of small-molecule CGRP receptor antagonists and monoclonal antibodies targeting either CGRP or its receptor.</p><p><strong>Areas covered: </strong>We will present selected aspects of the role of CGRP in the pathogenesis of migraine, the efficacy of CGRP-targeted treatment, and the still-open questions regarding the practical application of CGRP antagonists in headache medicine.</p><p><strong>Expert opinion: </strong>CGRP-targeting drugs represent a transformative approach to migraine treatment, offering superior efficacy and tolerability compared to traditional therapies, they are a helpful addition to the treatment arsenal but also have their flaws and require further observation. Their availability provides new hope for migraine patients, particularly those who have not responded adequately to conventional treatments. Future directions for migraine care planning, especially for chronic migraine and medication-overuse headache, should include universal access to these specific and effective forms of therapy to prevent complications from the disease and its negative effects in many aspects of a patient's life.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Plasma protein binding of arsenic species in acute promyelocytic leukemia patients and their relationships with hepatic and renal function. 急性早幼粒细胞白血病患者血浆蛋白中砷的结合力及其与肝肾功能的关系。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-18 DOI: 10.1080/17512433.2024.2417666
Chunlu Gao, Rui Duan, Shuo Tian, Chunrong Pang, Hong Zhang, Haixia Yang, Xin Hai

Objectives: Percentage protein binding (%PB) of arsenic species in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide remains unclear. It can be different depending on the status of hepatic or renal function.

Methods: This study obtained steady-state blood samples from normal APL patients and those with hepatic or renal impairment. %PB of inorganic arsenic (iAs), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) was determined by analyzing free and total plasma concentrations using ultrafiltration method by HPLC-HG-AFS.

Results: There is a linear relationship between free and total plasma concentrations for iAs (r2 = 0.952), MMAV (r2 = 0.603), and DMAV (r2 = 0.945). For patients with normal hepatic and renal function, mean %PB was as follows: iAs at 26.7 ± 14.3%, MMAV at 53.3 ± 11.9%, and DMAV at 24.7 ± 7.8%. %PB decreased in patients with renal impairment, with MMAV and DMAV showing statistically significant differences (p < 0.05 for MMAV, p < 0.01 for DMAV). No significant differences in %PB between normal and hepatic impairment group were observed.

Conclusion: Free arsenic species fraction can be estimated by total concentration. DMAV and iAs present low %PB, while MMAV exhibits a relatively high %PB in plasma. Level of %PB is more likely to be affected by renal function and age.

目的:接受三氧化二砷治疗的急性早幼粒细胞白血病(APL)患者体内砷的蛋白结合率(%PB)仍不清楚。方法:本研究采集了正常 APL 患者的稳态血液样本:本研究采集了正常 APL 患者和肝肾功能受损患者的稳态血样。方法:本研究采集了正常 APL 患者和肝肾功能受损患者的稳态血样,采用 HPLC-HG-AFS 超滤法分析游离和总血浆浓度,测定无机砷(iAs)、一甲基砷酸(MMAV)和二甲基砷酸(DMAV)的 PB%:结果:iAs(r2 = 0.952)、MMAV(r2 = 0.603)和 DMAV(r2 = 0.945)的游离浓度和血浆总浓度之间呈线性关系。肝肾功能正常患者的平均 PB 百分比如下:iAs 为 26.7 ± 14.3%,MMAV 为 53.3 ± 11.9%,DMAV 为 24.7 ± 7.8%。肾功能受损患者的血压百分比下降,MMAV 和 DMAV 显示出显著的统计学差异(p V,p V)。正常组和肝功能受损组的 PB 百分比无明显差异:结论:游离砷物种部分可通过总浓度估算。DMAV 和 iAs 的 PB 百分比较低,而 MMAV 在血浆中的 PB 百分比相对较高。PB%的水平更有可能受到肾功能和年龄的影响。
{"title":"Plasma protein binding of arsenic species in acute promyelocytic leukemia patients and their relationships with hepatic and renal function.","authors":"Chunlu Gao, Rui Duan, Shuo Tian, Chunrong Pang, Hong Zhang, Haixia Yang, Xin Hai","doi":"10.1080/17512433.2024.2417666","DOIUrl":"https://doi.org/10.1080/17512433.2024.2417666","url":null,"abstract":"<p><strong>Objectives: </strong>Percentage protein binding (%PB) of arsenic species in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide remains unclear. It can be different depending on the status of hepatic or renal function.</p><p><strong>Methods: </strong>This study obtained steady-state blood samples from normal APL patients and those with hepatic or renal impairment. %PB of inorganic arsenic (iAs), monomethylarsonic acid (MMA<sup>V</sup>), and dimethylarsinic acid (DMA<sup>V</sup>) was determined by analyzing free and total plasma concentrations using ultrafiltration method by HPLC-HG-AFS.</p><p><strong>Results: </strong>There is a linear relationship between free and total plasma concentrations for iAs (r<sup>2</sup> = 0.952), MMA<sup>V</sup> (r<sup>2</sup> = 0.603), and DMA<sup>V</sup> (r<sup>2</sup> = 0.945). For patients with normal hepatic and renal function, mean %PB was as follows: iAs at 26.7 ± 14.3%, MMA<sup>V</sup> at 53.3 ± 11.9%, and DMA<sup>V</sup> at 24.7 ± 7.8%. %PB decreased in patients with renal impairment, with MMA<sup>V</sup> and DMA<sup>V</sup> showing statistically significant differences (<i>p</i> < 0.05 for MMA<sup>V</sup>, <i>p</i> < 0.01 for DMA<sup>V</sup>). No significant differences in %PB between normal and hepatic impairment group were observed.</p><p><strong>Conclusion: </strong>Free arsenic species fraction can be estimated by total concentration. DMA<sup>V</sup> and iAs present low %PB, while MMA<sup>V</sup> exhibits a relatively high %PB in plasma. Level of %PB is more likely to be affected by renal function and age.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Methotrexate polyglutamates. 甲氨蝶呤多聚谷氨酸盐。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-15 DOI: 10.1080/17512433.2024.2416674
Zhilin Yang, Jiayi Mo, Wenshu Li, Zhigang Zhao, Shenghui Mei

Introduction: Methotrexate polyglutamates (MTXPGs) are intracellular metabolites of methotrexate (MTX) that play a critical role in the drug's activity, influencing both its efficacy and toxicity. As the exact implications of MTXPGs in these processes remain a subject of debate, a comprehensive review of MTXPGs could provide valuable insights for clinicians and pharmacists, potentially minimizing adverse reactions and enhancing therapeutic outcomes.

Areas covered: A comprehensive search of relevant literature was conducted in PubMed and Web of Science databases, including studies from their inception to April 2024. Eligible studies included reviews, clinical trials, and real-world analyses. Additional manual searches and citation reviews were also performed. This review aims to explore MTXPGs with a primary focus on their pharmacokinetics, analytical methods, determinants of drug exposure, and their correlation with MTX efficacy and toxicity.

Expert opinion: MTXPGs have not yet garnered significant attention in clinical practice. However, multiple studies have demonstrated a relationship between MTXPGs and the efficacy and toxicity of MTX, suggesting a potential avenue for personalized treatment strategies. Future research should aim to further validate and refine this correlation. Additionally, attention should also be directed toward other metabolites of MTX, which may hold clinical significance.

简介:甲氨蝶呤多聚谷氨酸盐(MTXPGs)是甲氨蝶呤(MTX)的细胞内代谢产物,在药物活性中起着至关重要的作用,影响着药物的疗效和毒性。由于 MTXPGs 在这些过程中的确切影响仍存在争议,因此对 MTXPGs 进行全面审查可为临床医生和药剂师提供有价值的见解,从而有可能最大限度地减少不良反应并提高治疗效果:在 PubMed 和 Web of Science 数据库中对相关文献进行了全面检索,包括从开始到 2024 年 4 月的研究。符合条件的研究包括综述、临床试验和真实世界分析。此外,还进行了其他人工检索和引文综述。本综述旨在探讨 MTXPGs,主要关注其药代动力学、分析方法、药物暴露的决定因素以及与 MTX 疗效和毒性的相关性:MTXPG尚未在临床实践中引起广泛关注。然而,多项研究表明,MTXPGs 与 MTX 的疗效和毒性之间存在关系,这为个性化治疗策略提供了潜在的途径。未来的研究应旨在进一步验证和完善这种相关性。此外,还应关注 MTX 的其他代谢物,它们可能具有临床意义。
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引用次数: 0
An overview on disease modifying and symptomatic drug treatments for multiple sclerosis. 多发性硬化症的改病和对症药物治疗概述。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-08 DOI: 10.1080/17512433.2024.2410393
Gloria Dalla Costa, Letizia Leocani, Mariaemma Rodegher, Luca Chiveri, Alessandro Gradassi, Giancarlo Comi

Introduction: Multiple sclerosis (MS) is an inflammatory and degenerative autoimmune condition, resulting frequently in a disabling condition. Significant improvements of long-term prognosis have been recently achieved with an early and more aggressive use of disease modifying therapies (DMTs). Addressing the complexity of managing its progressive forms remains a significant challenge.

Areas covered: This review provides an update on DMTs for relapsing-remitting MS (RRMS) and progressive MS and their efficacy, safety, and mechanism of action, emphasizing the critical role of biomarkers in optimizing treatment decisions. Moreover, some key information on drugs used to manage symptoms such as pain, fatigue, spasticity and urinary problems will be provided. The literature search was conducted using PubMed, Embase, and Cochrane Library databases covering the period from January 2000 to January 2024.

Expert opinion: Major advances have been achieved in the treatment of RRMS. Treatment should start immediately as soon as the neurologist is confident with the diagnosis and its choice should be based on the prognostic profile and on the patient's propensity to accept drug-related risks. The therapeutic landscape for progressive MS is quite disappointing and necessitates further innovation. Personalized medicine, leveraging biomarker insights, holds promise for refining treatment efficacy and patient outcomes.

导言:多发性硬化症(MS)是一种炎症性和变性的自身免疫性疾病,经常导致残疾。最近,通过早期和更积极地使用改变疾病疗法(DMTs),多发性硬化症的长期预后得到了显著改善。但如何应对渐进形式的复杂病情仍然是一项重大挑战:本综述提供了有关治疗复发性多发性硬化症(RRMS)和进展性多发性硬化症的 DMTs 及其疗效、安全性和作用机制的最新信息,强调了生物标志物在优化治疗决策中的关键作用。此外,还将提供一些用于控制疼痛、疲劳、痉挛和泌尿系统问题等症状的药物的关键信息。我们使用 PubMed、Embase 和 Cochrane Library 数据库对 2000 年 1 月至 2024 年 1 月期间的文献进行了检索:RRMS 的治疗已取得重大进展。一旦神经科医生确信诊断结果,就应立即开始治疗,治疗方案的选择应基于预后情况和患者接受药物相关风险的倾向。进展期多发性硬化症的治疗前景令人失望,需要进一步创新。利用生物标志物洞察力的个性化医疗有望改善治疗效果和患者预后。
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引用次数: 0
Tirzepatide, a novel, dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist for the ongoing diabesity epidemic: the dawn of a new era? 新型双重葡萄糖依赖性促胰岛素多肽/胰高血糖素样肽-1 受体激动剂 Tirzepatide:新时代的曙光?
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-04 DOI: 10.1080/17512433.2024.2408753
Imran Rangraze, Dimitrios Patoulias, Paschalis Karakasis, Mohamed El-Tanani, Manfredi Rizzo
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引用次数: 0
期刊
Expert Review of Clinical Pharmacology
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