Drugs最新文献

{"title":"Anticoagulation in Chronic Kidney Disease.","authors":"Marco Montomoli, Boris Gonzales Candía, Adriana Acosta Barrios, Elisa Perez Bernat","doi":"10.1007/s40265-024-02077-6","DOIUrl":"10.1007/s40265-024-02077-6","url":null,"abstract":"<p><p>The nuanced landscape of anticoagulation therapy in patients with chronic kidney disease (CKD) presents a formidable challenge, intricately balancing the dual hazards of hemorrhage and thrombosis. These patients find themselves in a precarious position, teetering on the edge of these risks due to compromised platelet functionality and systemic disturbances within their coagulation frameworks. The management of such patients necessitates a meticulous approach to dosing adjustments and vigilant monitoring to navigate the perilous waters of anticoagulant therapy. This is especially critical considering the altered pharmacokinetics in CKD, where the clearance of drugs is significantly impeded, heightening the risk of accumulation and adverse effects. In the evolving narrative of anticoagulation therapy, the introduction of direct oral anticoagulants (DOACs) has heralded a new era, offering a glimmer of hope for those navigating the complexities of CKD. These agents, with their promise of easier management and a reduced need for monitoring, have begun to reshape the contours of care, particularly for patients not yet on dialysis. However, this is not without its caveats. The application of DOACs in the context of advanced CKD remains a largely uncharted territory, necessitating a cautious exploration to unearth their true potential and limitations. Moreover, the advent of innovative strategies such as left atrial appendage occlusion (LAAO) underscores the dynamic nature of anticoagulation therapy, potentially offering a tailored solution for those at the intersection of CKD and elevated stroke risk. Yet the journey toward integrating such advancements into standard practice is laden with unanswered questions, demanding rigorous investigation to illuminate their efficacy and safety across the spectrum of kidney disease. In summary, the management of anticoagulation in CKD is a delicate dance, requiring a harmonious blend of precision, caution, and innovation. As we venture further into this complex domain, we must build upon our current understanding, embracing both emerging therapies and the need for ongoing research. Only then can we hope to offer our patients a path that navigates the narrow strait between bleeding and clotting, toward safer and more effective care.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1199-1218"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Donanemab: First Approval.","authors":"Connie Kang","doi":"10.1007/s40265-024-02103-7","DOIUrl":"10.1007/s40265-024-02103-7","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1335"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asthma and Cardiovascular Diseases: Navigating Mutual Pharmacological Interferences.","authors":"Mario Cazzola, Clive P Page, Nicola A Hanania, Luigino Calzetta, Maria Gabriella Matera, Paola Rogliani","doi":"10.1007/s40265-024-02086-5","DOIUrl":"10.1007/s40265-024-02086-5","url":null,"abstract":"<p><p>Asthma and cardiovascular disease (CVD) often co-exist. When a patient has both conditions, management requires an approach that addresses the unique challenges of each condition separately, while also considering their potential interactions. However, specific guidance on the management of asthma in patients with CVD and on the management of CVD in patients with asthma is still lacking. Nevertheless, health care providers need to adopt a comprehensive approach that includes both respiratory and CVD health. The management of CVD in patients with asthma requires a delicate balance between controlling respiratory symptoms and minimising potential cardiovascular (CV) risks. In the absence of specific guidelines for the management of patients with both conditions, the most prudent approach would be to follow established guidelines for each condition independently. Careful selection of asthma medications is essential to avoid exacerbation of CV symptoms. In addition, optimal management of CV risk factors is essential. However, close monitoring of these patients is important as there is evidence that some asthma medications may have adverse effects on CVD and, conversely, that some CVD medications may worsen asthma symptoms. On the other hand, there is also increasing evidence of the potential beneficial effects of asthma medications on CVD and, conversely, that some CVD medications may reduce the severity of asthma symptoms. We aim to elucidate the potential risks and benefits associated with the use of asthma medications in patients with CVD, and the potential pulmonary risks and benefits for patients with asthma who are prescribed CVD medications.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1251-1273"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cefepime-Taniborbactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination.","authors":"George G Zhanel, Celine Mansour, Stacey Mikolayanko, Courtney K Lawrence, Sheryl Zelenitsky, Danyel Ramirez, Frank Schweizer, Denice Bay, Heather Adam, Philippe Lagacé-Wiens, Andrew Walkty, Neal Irfan, Nina Clark, David Nicolau, Carlo Tascini, James A Karlowsky","doi":"10.1007/s40265-024-02082-9","DOIUrl":"10.1007/s40265-024-02082-9","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Taniborbactam (formerly known as VNRX-5133) is a novel bicyclic boronate β-lactamase inhibitor of serine β-lactamases (SBLs) [Ambler classes A, C, and D] and metallo-β-lactamases (MBLs) [Ambler class B], including NDM and VIM, but not IMP. Cefepime-taniborbactam is active in vitro against most isolates of carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA), including both carbapenemase-producing and carbapenemase-non-producing CRE and CRPA, as well as against multidrug-resistant (MDR), ceftazidime-avibactam-resistant, meropenem-vaborbactam-resistant, and ceftolozane-tazobactam-resistant Enterobacterales and P. aeruginosa. The addition of taniborbactam to cefepime resulted in a &gt; 64-fold reduction in MIC&lt;sub&gt;90&lt;/sub&gt; compared with cefepime alone for a 2018-2021 global collection of &gt; 13,000 clinical isolates of Enterobacterales. In the same study, against &gt; 4600 P. aeruginosa, a fourfold MIC reduction was observed with cefepime-taniborbactam, compared with cefepime alone. Whole genome sequencing studies have shown that resistance towards cefepime-taniborbactam in Enterobacterales arises due to the presence of multiple resistance mechanisms, often in concert, including production of IMP, PBP3 alterations, permeability (porin) defects, and upregulation of efflux pumps. In P. aeruginosa, elevated cefepime-taniborbactam MICs are also associated with the presence of multiple, concurrent mechanisms, most frequently IMP, PBP3 mutations, and upregulation of efflux pumps, as well as AmpC (PDC) overexpression. The pharmacokinetics of taniborbactam are dose proportional, follow a linear model, and do not appear to be affected when combined with cefepime. Taniborbactam's approximate volume of distribution (V&lt;sub&gt;d&lt;/sub&gt;) at steady state is 20 L and the approximate elimination half-life (t&lt;sub&gt;½&lt;/sub&gt;) is 2.3 h, which are similar to cefepime. Furthermore, like cefepime, taniborbactam is primarily cleared renally, and clearance corresponds with renal function. Pharmacodynamic studies (in vitro and in vivo) have reported that cefepime-taniborbactam has bactericidal activity against various β-lactamase-producing Gram-negative bacilli that are not susceptible to cefepime alone. It has been reported that antimicrobial activity best correlated with taniborbactam exposure (area under the curve). A phase III clinical trial showed that cefepime-taniborbactam (2 g/0.5 g administered as an intravenous infusion over 2 h) was superior to meropenem for the treatment of complicated urinary tract infection (cUTI), including acute pyelonephritis, caused by Enterobacterales species and P. aeruginosa while demonstrating similar safety compared with meropenem. The safety and tolerability of taniborbactam and cefepime-taniborbactam has been reported in one pharmacokinetic trial, and in two pharmacokinetic trials and one phase III clinical trial, respectively. Cefepime-taniborbactam appears to be well tolerated in both healthy su","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1219-1250"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Zastaprazan: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-024-02093-6","DOIUrl":"10.1007/s40265-024-02093-6","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1333"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vorasidenib: First Approval.","authors":"Yvette N Lamb","doi":"10.1007/s40265-024-02097-2","DOIUrl":"10.1007/s40265-024-02097-2","url":null,"abstract":"<p><p>Vorasidenib (VORANIGO^®; Servier) is an orally administered, first-in-class, highly brain-penetrant dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 (IDH1/2) enzymes being developed for use in IDH-mutant diffuse glioma. Vorasidenib received its first approval on 6 August 2024, in the USA, for the treatment of adult and pediatric patients aged 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery, including biopsy, sub-total resection, or gross total resection. Approval was based on results from the multinational phase III INDIGO trial, in which vorasidenib significantly improved progression-free survival and time to the next anticancer intervention relative to placebo. In the EU and other countries worldwide, regulatory review of vorasidenib in IDH-mutant glioma is currently underway. This article summarizes the milestones in the development of vorasidenib leading to this first approval for glioma.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1325-1331"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose Individualisation of Antimicrobials from a Pharmacometric Standpoint: The Current Landscape.","authors":"Tim Preijers, Anouk E Muller, Alan Abdulla, Brenda C M de Winter, Birgit C P Koch, Sebastiaan D T Sassen","doi":"10.1007/s40265-024-02084-7","DOIUrl":"10.1007/s40265-024-02084-7","url":null,"abstract":"<p><p>Successful antimicrobial therapy depends on achieving optimal drug concentrations within individual patients. Inter-patient variability in pharmacokinetics (PK) and differences in pathogen susceptibility (reflected in the minimum inhibitory concentration, [MIC]) necessitate personalised approaches. Dose individualisation strategies aim to address this challenge, improving treatment outcomes and minimising the risk of toxicity and antimicrobial resistance. Therapeutic drug monitoring (TDM), with the application of population pharmacokinetic (popPK) models, enables model-informed precision dosing (MIPD). PopPK models mathematically describe drug behaviour across populations and can be combined with patient-specific TDM data to optimise dosing regimens. The integration of machine learning (ML) techniques promises to further enhance dose individualisation by identifying complex patterns within extensive datasets. Implementing these approaches involves challenges, including rigorous model selection and validation to ensure suitability for target populations. Understanding the relationship between drug exposure and clinical outcomes is crucial, as is striking a balance between model complexity and clinical usability. Additionally, regulatory compliance, outcome measurement, and practical considerations for software implementation will be addressed. Emerging technologies, such as real-time biosensors, hold the potential for revolutionising TDM by enabling continuous monitoring, immediate and frequent dose adjustments, and near patient testing. The ongoing integration of TDM, advanced modelling techniques, and ML within the evolving digital health care landscape offers a potential for enhancing antimicrobial therapy. Careful attention to model development, validation, and ethical considerations of the applied techniques is paramount for successfully optimising antimicrobial treatment for the individual patient.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1167-1178"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Golidocitinib: First Approval","authors":"Susan J. Keam","doi":"10.1007/s40265-024-02089-2","DOIUrl":"https://doi.org/10.1007/s40265-024-02089-2","url":null,"abstract":"<p>Golidocitinib (高瑞哲^®) is an oral, potent, selective Janus kinase 1 (JAK1) inhibitor being developed by Dizal (Jiangsu) Pharmaceutical Co., Ltd for the treatment of cancer, including peripheral T cell lymphoma (PTCL). In June 2024, golidocitinib received conditional approval in China for the treatment of adult patients with relapsed or refractory (r/r) PTCL who have received at least one line of systemic treatment. This article summarizes the milestones in the development of golidocitinib leading to this first approval for the treatment of adults with PTCL.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":"86 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Slowing the Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Using Four Pillars of Therapy: The Time to Act is Now","authors":"Panagiotis I. Georgianos, Vasilios Vaios, Theocharis Koufakis, Vassilios Liakopoulos","doi":"10.1007/s40265-024-02091-8","DOIUrl":"https://doi.org/10.1007/s40265-024-02091-8","url":null,"abstract":"<p>Chronic kidney disease (CKD) is the most common co-morbidity in patients with type 2 diabetes (T2D) and its presence substantially amplifies the risk for premature death, adverse cardiovascular events, and faster progression of kidney injury to kidney failure. For nearly two decades, the pharmacological blockade of the renin-angiotensin-system (RAS) was the only pillar of therapy to afford cardiorenal protection in these patients. During the last 5 years, newer novel therapies have been added to our therapeutic armamentarium, offering promise for more effective management of diabetic kidney disease in the future. Large phase 3 clinical trials have demonstrated additive cardiorenal protective benefits of sodium-glucose co-transporter type 2 (SGLT-2) inhibitors, the non-steroidal mineralocorticoid-receptor-antagonist (MRA) finerenone, and glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide relative to placebo in patients with albuminuric CKD and T2D who are receiving standard-of-care treatment with a RAS-blocker. These therapies are likely much more effective when administered in a combined therapeutic algorithm, but the potential additive effects of combination therapy remain to be established in ongoing clinical trials. In this article, we assemble four pillars of therapy for the attenuation of residual cardiorenal risk in patients with CKD associated with T2D. We provide evidence from recent randomized trials and we discuss the concept of combined treatment for maximal cardiorenal protection in this high-risk patient population.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":"3 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting DNA Damage Response Deficiency in Thoracic Cancers.","authors":"Aleksandra Bzura, Jake B Spicer, Sean Dulloo, Timothy A Yap, Dean A Fennell","doi":"10.1007/s40265-024-02066-9","DOIUrl":"10.1007/s40265-024-02066-9","url":null,"abstract":"<p><p>Thoracic cancers comprise non-small cell lung cancers (NSCLCs), small cell lung cancers (SCLCs) and malignant pleural mesotheliomas (MPM). Collectively, they account for the highest rate of death from malignancy worldwide. Genomic instability is a universal feature of cancer, which fuels mutations and tumour evolution. Deficiencies in DNA damage response (DDR) genes amplify genomic instability. Homologous recombination deficiency (HRD), resulting from BRCA1/BRCA2 inactivation, is exploited for therapeutic synthetic lethality with poly-ADP ribose polymerase (PARP) inhibitors in breast and ovarian cancers, as well as in prostate and pancreatic cancers. However, DDR deficiency and its therapeutic implications are less well established in thoracic cancers. Emerging evidence suggests that a subset of thoracic cancers may harbour DDR deficiency and may, thus, be effectively targeted with DDR agents. Here, we review the current evidence surrounding DDR in thoracic cancers and discuss the challenges and promise for achieving clinical benefit with such therapeutics.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1025-1033"},"PeriodicalIF":13.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}