Pub Date : 2024-10-29DOI: 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.
{"title":"Messenger interference RNA therapies targeting apolipoprotein C-III and angiopoietin-like protein 3 for mixed hyperlipidemia: the future of plozasiran and zodasiran.","authors":"Zonghao Pan, Muhammad Adnan Zaman, Sidra Kalsoom, Yani Zhang","doi":"10.1080/17512433.2024.2423724","DOIUrl":"10.1080/17512433.2024.2423724","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521483","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}
Pub Date : 2024-10-27DOI: 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.
{"title":"SGLT2i and GLP1RA effects in patients followed in a hospital diabetology consultation.","authors":"António Cabral Lopes, Olga Lourenço, Manuel Morgado","doi":"10.1080/17512433.2024.2421872","DOIUrl":"https://doi.org/10.1080/17512433.2024.2421872","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Research design and methods: </strong>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).</p><p><strong>Results: </strong>Patients treated with SGLT2i exhibited a significant improvement in eGFR at the endpoint compared to baseline (<i>p</i> = 0.006). Both treatment groups experienced reductions in systolic blood pressure at the endpoint; especially patients treated with SGLT2i (<i>p</i> = 0.0002). GLP1RA treatment resulted in a statistically significant weight reduction from baseline to endpoint (<i>p</i> < 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 (<i>p</i> = 0.004 and <i>p</i> = 0.002, respectively). Additionally, both treatments were associated with a significant reduction in HbA1c levels at the endpoint (<i>p</i> = 0.010 and <i>p</i> = 0.002, respectively).</p><p><strong>Conclusions: </strong>Our findings suggest that SGLT2i and GLP1RA offer beneficial effects in patients with T2DM.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497733","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}
Pub Date : 2024-10-23DOI: 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.
{"title":"Renin-angiotensin system inhibition and mortality in patients undergoing dialysis with coronary artery disease: insights from a multi-center observational study.","authors":"Enmin Xie, Shuoyan An, Yaxin Wu, Zixiang Ye, Xuecheng Zhao, Yike Li, Nan Shen, Yanxiang Gao, Jingang Zheng","doi":"10.1080/17512433.2024.2419915","DOIUrl":"10.1080/17512433.2024.2419915","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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, <i>p</i> < 0.001) and cardiovascular death (17.0% vs 23.8%; HR 0.64, 95% CI 0.48-0.83, <i>p</i> = 0.001). These findings remained consistent across IPTW and PSM analyses. Sensitivity analyses for ACEI and ARB use separately yielded similar results.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461438","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}
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.
{"title":"Semaglutide and smoking cessation in individuals with type 2 diabetes mellitus: there is no smoke without fire!","authors":"Djordje S Popovic, Dimitrios Patoulias, Theocharis Koufakis, Paschalis Karakasis, Ieva Ruža, Nikolaos Papanas","doi":"10.1080/17512433.2024.2418398","DOIUrl":"https://doi.org/10.1080/17512433.2024.2418398","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461439","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}
Pub Date : 2024-10-19DOI: 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.
{"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}
Pub Date : 2024-10-18DOI: 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.
{"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}
Pub Date : 2024-10-18DOI: 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.
{"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}
Pub Date : 2024-10-15DOI: 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.
{"title":"Methotrexate polyglutamates.","authors":"Zhilin Yang, Jiayi Mo, Wenshu Li, Zhigang Zhao, Shenghui Mei","doi":"10.1080/17512433.2024.2416674","DOIUrl":"10.1080/17512433.2024.2416674","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399864","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}
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.
{"title":"An overview on disease modifying and symptomatic drug treatments for multiple sclerosis.","authors":"Gloria Dalla Costa, Letizia Leocani, Mariaemma Rodegher, Luca Chiveri, Alessandro Gradassi, Giancarlo Comi","doi":"10.1080/17512433.2024.2410393","DOIUrl":"https://doi.org/10.1080/17512433.2024.2410393","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389219","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}
{"title":"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?","authors":"Imran Rangraze, Dimitrios Patoulias, Paschalis Karakasis, Mohamed El-Tanani, Manfredi Rizzo","doi":"10.1080/17512433.2024.2408753","DOIUrl":"10.1080/17512433.2024.2408753","url":null,"abstract":"","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371405","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}