Clinical Pharmacology : Advances and Applications最新文献

{"title":"Exenatide Once Weekly for Management of Type 2 Diabetes: A Review","authors":"Jun Inaishi, Y. Saisho","doi":"10.2147/CPAA.S288846","DOIUrl":"https://doi.org/10.2147/CPAA.S288846","url":null,"abstract":"Abstract Exenatide is one of the exendin-based glucagon-like peptide 1 receptor agonists (GLP-1RAs) and is currently available in two formulations, ie, exenatide twice daily (BID), a short-acting GLP-1RA, and exenatide once weekly (QW), a long-acting GLP-1RA. Clinical efficacy and safety of exenatide 2 mg QW in patients with type 2 diabetes (T2DM) has been demonstrated in the DURATION study program. Exenatide QW has been shown to achieve greater HbA1c reduction compared with exenatide BID, with less injection frequency and greater treatment satisfaction. However, exenatide QW failed to show a significant cardiovascular risk reduction in a cardiovascular outcome trial (CVOT), the EXSCEL trial, while other GLP-1RAs have shown positive CV outcomes. Furthermore, exenatide QW has been shown to be inferior to liraglutide and semaglutide with respect to HbA1c or body weight reduction in the head-to-head trials. Thus, although the long-term efficacy and safety of exenatide QW have been demonstrated, exenatide QW might be selected with lower priority within the class of GLP1-RAs for the management of T2DM, especially for patients at high CV risk. On the other hand, exenatide QW is now expected to be a treatment option for children with T2DM or patients with Parkinson’s disease. This review provides an overview of the current evidence regarding the clinical efficacy and safety of exenatide QW and discusses the current perspectives on exenatide QW for treatment of T2DM.","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"14 1","pages":"19 - 26"},"PeriodicalIF":2.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41643553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antileishmanial Activity of Tamoxifen by Targeting Sphingolipid Metabolism: A Review","authors":"Kaleab Alemayehu Zewdie, Haftom Gebregergs Hailu, M. A. Ayza, B. Tesfaye","doi":"10.2147/CPAA.S344268","DOIUrl":"https://doi.org/10.2147/CPAA.S344268","url":null,"abstract":"Abstract Leishmaniasis is a widespread group of neglected parasitic diseases caused by protozoa of the genus Leishmania. Around 2 million new cases are reported each year and around 12 million people are at risk of being infected. Although various therapies have been used to treat leishmaniasis, they have been associated with increased cytotoxicity and drug resistance problems. Hence, the present review was intended to show the potential of tamoxifen as an alternative option for the treatment of leishmaniasis. Tamoxifen is a known selective estrogen receptor modulator and has been widely used for the treatment of early-stage breast cancer. Various experimental and clinical studies revealed that it has an antileishmanial effect by decreasing parasitic burden, with low cost and few side effects. The antileishmanial action of tamoxifen has been related to its potential effect on sphingolipid metabolism. Besides, it affects mitochondrial function by inducing alterations in the plasma membrane potential. However, further detailed studies are required to show the ultimate effects on health outcomes.","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"14 1","pages":"11 - 17"},"PeriodicalIF":2.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41979156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Response to Article \"Anti-Diarrheal Activity of Hydromethanolic Crude Extract and Solvent Fractions of Acacia Seyal (Fabaceae) Roots in Mice\" [Letter].","authors":"Novaria Sari Dewi Panjaitan, Fitriana Fitriana, Sarwo Handayani","doi":"10.2147/CPAA.S398217","DOIUrl":"https://doi.org/10.2147/CPAA.S398217","url":null,"abstract":"of anti-diarrheal","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"14 ","pages":"111-112"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/93/cpaa-14-111.PMC9719282.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10344845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Diarrheal Activities of Hydromethanolic Crude Extract and Solvent Fractions of <i>Acacia seyal</i> (Fabaceae) Roots in Mice [Response to Letter].","authors":"Assefa Kebad Mengesha,&nbsp;Eshetie Melese Birru,&nbsp;Meaza Adugna","doi":"10.2147/CPAA.S400000","DOIUrl":"https://doi.org/10.2147/CPAA.S400000","url":null,"abstract":"","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"14 ","pages":"113-114"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/55/cpaa-14-113.PMC9744855.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10731619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Net Modeling of Checkpoint Inhibitor Related Myocarditis and Steroid Response.","authors":"Filip Stefanovic,&nbsp;Andres Gomez-Caminero,&nbsp;David M Jacobs,&nbsp;Poornima Subramanian,&nbsp;Igor Puzanov,&nbsp;Maya R Chilbert,&nbsp;Steven G Feuerstein,&nbsp;Yan Yatsynovich,&nbsp;Benjamin Switzer,&nbsp;Jerome J Schentag","doi":"10.2147/CPAA.S369008","DOIUrl":"https://doi.org/10.2147/CPAA.S369008","url":null,"abstract":"<p><strong>Background: </strong>Serious but rare side effects associated with immunotherapy pose a difficult problem for regulators and practitioners. Immune checkpoint inhibitors (ICIs) have come into widespread use in oncology in recent years and are associated with rare cardiotoxicity, including potentially fatal myocarditis. To date, no comprehensive model of myocarditis progression and outcomes integrating time-series based laboratory and clinical signals has been constructed. In this paper, we describe a time-series neural net (NN) model of ICI-related myocarditis derived using supervised machine learning.</p><p><strong>Methods: </strong>We extracted and modeled data from electronic medical records of ICI-treated patients who had an elevation in their troponin. All data collection was performed using an electronic case report form, with approximately 300 variables collected on as many occasions as available, yielding 6000 data elements per patient over their clinical course. Key variables were scored 0-5 and sequential assessments were used to construct the model. The NN model was developed in MatLab and applied to analyze the time course and outcomes of treatments.</p><p><strong>Results: </strong>We identified 23 patients who had troponin elevations related to their ICI therapy, 15 of whom had ICI-related myocarditis, while the remaining 8 patients on ICIs had other causes for troponin elevation, such as myocardial infarction. Our model showed that troponin was the most predictive biomarker of myocarditis, in line with prior studies. Our model also identified early and aggressive use of steroid treatment as a major determinant of survival for cases of grade 3 or 4 ICI-related myocarditis.</p><p><strong>Conclusion: </strong>Our study shows that a supervised learning NN can be used to model rare events such as ICI-related myocarditis and thus provide clinical insight into drivers of progression and treatment outcomes. These findings direct attention to early detection biomarkers and clinical symptoms as the best means of implementing early and potentially life-saving steroid treatment.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"14 ","pages":"69-90"},"PeriodicalIF":2.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/8c/cpaa-14-69.PMC9376002.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10589798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Assessing Efficacy and Safety of a Novel Low-Dose Turmeric Extract Formulation in Healthy Adults with Chronic Knee Pain.","authors":"Shefali Thanawala, Rajat Shah, Venkateswarlu Somepalli, KrishnaRaju Venkata Alluri, Prabakaran Desomayanandam, Arun Bhuvanendran","doi":"10.2147/CPAA.S307464","DOIUrl":"10.2147/CPAA.S307464","url":null,"abstract":"<p><strong>Background: </strong>Knee pain causes functional limitations, eventually compromising the quality of life. We evaluated the efficacy of our water-dispersible turmeric formulation (60% natural curcuminoids, TurmXTRA 60N^®-WDTE60N), which exhibited better PK profile at low dose (250 mg) than standard turmeric extract, in alleviating symptoms of chronic knee pain.</p><p><strong>Methods: </strong>In this randomized, double-blind, placebo-controlled trial, subjects received either 250 mg WDTE60N capsule (150 mg curcuminoids; n = 53) or appearance-matched placebo capsule (n = 53) once daily for 90 days. Primary endpoint was change in pain score on the visual analogue scale (VAS) after 80-m fast-paced walk test.</p><p><strong>Results: </strong>A total of 96 subjects completed the study. WDTE60N reduced VAS score from baseline (5.4 ± 0.9) to day 90 (3.8 ± 0.8) with greater mean reduction than placebo (-1.5 ± 0.7 vs -0.6 ± 0.8, <i>p</i> < 0.0001; 2.5 times). It also significantly improved the time taken for 80-m fast-paced walk test and 9-step stair-climb test; and improved all biomarkers compared to placebo (<i>p</i> > 0.05). Three adverse events occurred but were unrelated to study products.</p><p><strong>Conclusion: </strong>WDTE60N 250 mg administered once daily for 3 months, alleviated knee pain, improved joint function in healthy subjects with chronic knee pain, was well tolerated and safe.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"13 ","pages":"91-100"},"PeriodicalIF":3.1,"publicationDate":"2021-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/ad/cpaa-13-91.PMC8149286.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9727011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wound Healing Effect of <i>Acokanthera schimperi</i> Schweinf (Apocynaceae) Methanol Leaf Extract Ointment in Mice and Its in-vitro Antioxidant Activity.","authors":"Belete Kassa Alemu,&nbsp;Desye Misganaw,&nbsp;Getnet Mengistu","doi":"10.2147/CPAA.S288394","DOIUrl":"https://doi.org/10.2147/CPAA.S288394","url":null,"abstract":"<p><strong>Background: </strong><i>Acokanthera schimperi</i> is traditionally used for the treatment of wounds and various bacterial infections. Due to the ongoing escalation of antimicrobial resistance, there is an increasing demand for the appropriate wound care and hence, the present study was initiated to investigate the wound healing effects of the leaf extract ointments of <i>A. schimperi</i> in mice and its in-vitro antioxidant activity.</p><p><strong>Methods: </strong>The crude extract was prepared as 5% and 10% w/w ointments for topical use in mice. Wound contraction and epithelialization period were determined in excision and infected models, whereas tensile strength was determined in an incision model. Besides, its antioxidant activity was evaluated using the DPPH method.</p><p><strong>Results: </strong>In this study, the 10% w/w extract ointment did not cause toxicity at the 2000 mg/kg limit dose. In the excision model, the 10% w/w ointment exhibited a significant wound contraction effect starting from day 6 to 14 with a complete epithelization shown on day 13. Besides, the 5%w/w ointment showed a significant wound contraction effect starting from day 6 onwards, and a significant decrease in the epithelization period observed on day 16. Conversely, both the 10% w/w and 5% w/w ointments showed significant wound contraction effects starting from day 4 and onwards in the infected model. However, a complete epithelization period was observed on days 14 and 18 in the 10%w/w and 5% w/w/extract ointment treated groups, respectively. In the incision model, the 10% (w/w) and 5% (w/w) extract ointments showed a significant increase in tensile strength by 36.80 and 32.23%, respectively. Moreover, the antioxidant activity of the extract was concentration-dependent with an IC50 value of 5.49± 0.38 µg/µL.</p><p><strong>Conclusion: </strong>The potential wound healing effects of this plant may provide a candidate source in the discovery of new drugs for the treatment of wounds.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"213-222"},"PeriodicalIF":2.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/c6/cpaa-12-213.PMC7780988.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38791306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Up-to-Date Overview of Therapeutic Agents for the Treatment of COVID-19 Disease.","authors":"Tafere Mulaw Belete","doi":"10.2147/CPAA.S284809","DOIUrl":"10.2147/CPAA.S284809","url":null,"abstract":"<p><p>Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a great potential to overwhelm the world healthcare systems that may lead to high morbidity and mortality. It also affects world economic development in the future. Currently, no proven effective drugs or vaccines are available for the management of COVID-19 disease. The pace of normal drug development progression is unacceptable in the context of the current pandemic. Therefore, repurposing the existing drugs that were used for the treatment of malaria, Ebola, and influenza helps rapid drug development for COVID-19. Currently, several repurposing candidate drugs are in a clinical trial including, chloroquine monoclonal antibodies, convalescent plasma, interferon, and antiviral therapies. Antiviral drugs like arbidol, remdesiv and favirnavir are the most promising due to the similarities of the viruses regarding viral entry, fusion, uncoating, and replication. This review article provides an overview of the potential therapeutic agent, which displayed better clinical treatment outcomes. Moreover, with further understanding of the SARS-CoV-2 virus, new drugs targeting specific SARS-CoV-2 viral components arise, and investigations on these novels anti-SARSCoV- 2 agents are also reviewed.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"203-212"},"PeriodicalIF":2.0,"publicationDate":"2020-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/3f/cpaa-12-203.PMC7753885.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38750941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Tolerability of PCSK9 Inhibitors: Current Insights.","authors":"Constantine E Kosmas,&nbsp;Andreas Skavdis,&nbsp;Andreas Sourlas,&nbsp;Evangelia J Papakonstantinou,&nbsp;Edilberto Peña Genao,&nbsp;Rogers Echavarria Uceta,&nbsp;Eliscer Guzman","doi":"10.2147/CPAA.S288831","DOIUrl":"https://doi.org/10.2147/CPAA.S288831","url":null,"abstract":"<p><p>The current era of preventive cardiology continues to emphasize on low-density lipoprotein cholesterol (LDL-C) reduction to alleviate the burden of atherosclerotic cardiovascular disease (ASCVD). In this regard, the pharmacological inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme via monoclonal antibodies has emerged as a novel lipid-lowering therapy, leading to a marked reduction in circulating LDL-C levels and subsequent improvement of cardiovascular outcomes. As these agents are increasingly used in current clinical practice, mounting scientific and clinical evidence supports that PCSK9 inhibitors offer an excellent safety and tolerability profile with a low incidence of adverse events. Notably, the most frequently reported side effects are injection-site reactions. In contrast to statins, PCSK9 inhibitors do not appear to exert a detrimental effect on glycemic control or to increase the incidence of new-onset diabetes mellitus. Accumulating evidence also indicates that PCSK9 inhibitors are a safe, well-tolerated and effective therapeutic strategy for patients with statin intolerance. On the other hand, as PCSK9 inhibitors reduce LDL-C to unprecedented low levels, a large body of current research has examined the effects of their long-term administration on neurocognition and on levels of vitamin E and other fat-soluble vitamins, providing encouraging results. This review aims to present and discuss the current clinical and scientific evidence pertaining to the safety and tolerability of PCSK9 inhibitors.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"191-202"},"PeriodicalIF":2.0,"publicationDate":"2020-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S288831","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38386556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Bodyweight-Based Dosing Truly Better Than Flat Dosing for Panitumumab? [Response to Letter].","authors":"Michael Z Liao,&nbsp;Johannes Kast,&nbsp;Marloes Berkhout,&nbsp;Hans Prenen,&nbsp;Sandeep Dutta,&nbsp;Vijay V Upreti","doi":"10.2147/CPAA.S289793","DOIUrl":"https://doi.org/10.2147/CPAA.S289793","url":null,"abstract":"","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"12 ","pages":"189-190"},"PeriodicalIF":2.0,"publicationDate":"2020-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/42/cpaa-12-189.PMC7734040.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38722248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}