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":"Current Insights on the Treatment of Anaplastic Lymphoma Kinase-Positive Metastatic Non-Small Cell Lung Cancer: Focus on Brigatinib.","authors":"Erika Rijavec,&nbsp;Federica Biello,&nbsp;Alice Indini,&nbsp;Francesco Grossi,&nbsp;Carlo Genova","doi":"10.2147/CPAA.S284850","DOIUrl":"https://doi.org/10.2147/CPAA.S284850","url":null,"abstract":"<p><p>Rearrangement of anaplastic lymphoma kinase (<i>ALK</i>) gene is detected in approximately 5% of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors targeting ALK have significantly improved the prognosis of these patients. However, most patients experienced disease progression within a few years due to acquired resistance. Brigatinib is a second-generation ALK inhibitor effective in presence of several <i>ALK</i> mutations with demonstrated activity against central nervous system metastases. Currently, brigatinib is approved to treat ALK-positive metastatic NSCLC patients not previously treated with ALK inhibitors and patients who have progressed on or are intolerant to crizotinib. In this review, we provide a summary of results from clinical trials involving brigatinib, and we discuss its possible role in the management of ALK-positive NSCLC in the following years.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"1-9"},"PeriodicalIF":2.0,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/1e/cpaa-14-1.PMC8786362.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39739095","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 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,&nbsp;Fitriana Fitriana,&nbsp;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":"Pharmacological Profile of Viltolarsen for the Treatment of Duchenne Muscular Dystrophy: A Japanese Experience.","authors":"Rohini Roy Roshmi,&nbsp;Toshifumi Yokota","doi":"10.2147/CPAA.S288842","DOIUrl":"https://doi.org/10.2147/CPAA.S288842","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is a fatal, X-linked recessive disorder characterized by progressive muscle loss and cardiorespiratory complications. Mutations in the <i>DMD</i> gene that eliminate the production of dystrophin protein are the underlying causes of DMD. Viltolarsen is a drug of phosphorodiamidate morpholino oligomer (PMO) chemistry, designed to skip exon 53 of the <i>DMD</i> gene. It aims to produce truncated but partially functional dystrophin in DMD patients and restore muscle function. Based on a preclinical study showing the ability of antisense PMOs targeting the DMD gene to improve muscle function in a large animal model, viltolarsen was developed by Nippon Shinyaku and the National Center of Neurology and Psychiatry in Japan. Following clinical trials conducted in Japan, Canada, and the United States showing significant improvements in muscle function, viltolarsen was approved for medical use in Japan in March 2020 and the United States in August 2020, respectively. Viltolarsen is a mutation-specific drug and will work for 8% of the persons with DMD who carry mutations amenable to exon 53 skipping. This review summarizes the pharmacological profile of viltolarsen, important clinical trials, and challenges, focusing on the contribution of Japanese patients and researchers in its development.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"235-242"},"PeriodicalIF":2.0,"publicationDate":"2021-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/81/aa/cpaa-13-235.PMC8688746.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39836901","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":"Potential of Quinine Sulfate for COVID-19 Treatment and Its Safety Profile: Review.","authors":"Irma Rahayu Latarissa,&nbsp;Melisa Intan Barliana,&nbsp;Anna Meiliana,&nbsp;Keri Lestari","doi":"10.2147/CPAA.S331660","DOIUrl":"https://doi.org/10.2147/CPAA.S331660","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic is currently the largest and most serious health crisis in the world. There is no definitive treatment for COVID-19. Vaccine administration has begun in various countries, but no vaccine is 100% effective. Some people are not protected after vaccination, and there are some groups of people who cannot be vaccinated therefore, research on COVID-19 treatment still needs to be done. Of the several drugs under study, chloroquine (CQ) and hydroxychloroquine (HCQ) are quite controversial, although they have good activity against SARS-CoV-2, both drugs have serious side effects. Indonesia with its wealth of natural ingredients has one potential compound, quinine sulfate (QS), which has the same structure and activity as CQ and HCQ and a better safety profile. The aim of this article was to review the potential of QS against the SARS-Cov-2 virus and outline its safety profile. We conclude that QS has the potential to be developed as a COVID-19 treatment with a better safety profile than that of CQ and HCQ.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"225-234"},"PeriodicalIF":2.0,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/be/cpaa-13-225.PMC8665662.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39815437","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 Case of Thrombocytosis Associated with Enoxaparin Therapy in an Adolescent.","authors":"Robert Murray,&nbsp;Joseph T Tobias","doi":"10.2147/CPAA.S327541","DOIUrl":"https://doi.org/10.2147/CPAA.S327541","url":null,"abstract":"<p><p>Secondary thrombocytosis, often referred to as a reactive thrombocytosis, is more common than primary thrombocytosis and has many potential etiologies including anemia, infection, inflammation, medications, and post-splenectomy. When considering the critically ill patient in the ICU setting potential medication-related etiologies of thrombocytosis should be included in the differential diagnosis. We present a 15-year-old adolescent with a traumatic brain injury who developed thrombocytosis that was temporally related to the administration of enoxaparin. There was a prompt return of the platelet count to normal following the discontinuation of enoxaparin therapy which led to the probable diagnosis of enoxaparin-induced thrombocytosis.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"203-207"},"PeriodicalIF":2.0,"publicationDate":"2021-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2d/f9/cpaa-13-203.PMC8536840.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39569976","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":"Comparing the Efficacy of a Nurse-Driven and a Physician-Driven Diabetic Ketoacidosis (DKA) Treatment Protocol.","authors":"Takla R Anis,&nbsp;Marybeth Boudreau,&nbsp;Tyson Thornton","doi":"10.2147/CPAA.S334119","DOIUrl":"https://doi.org/10.2147/CPAA.S334119","url":null,"abstract":"<p><strong>Background: </strong>Standardized DKA treatment could result in better overall safety and efficacy outcomes. The primary objective of this study is to validate the efficacy of an adapted nurse-driven DKA protocol compared to a physician-driven DKA protocol across the continuum of three hospital settings: the University of Colorado upon which the physician-driven protocol is based, Northern Light Eastern Maine Medical Center (NLEMMC), and Northern Light Sebasticook Valley Hospital (NLSVH). The secondary objective is to assess the safety of the adapted nurse-driven DKA protocol adapted at NLEMMC and NLSVH through determining the incidence of hypoglycemia and anion gap reopening.</p><p><strong>Patients and methods: </strong>This was a retrospective, IRB-approved, multi-center study that included: patients 18 years or older who were treated with the DKA protocol at NLEMMC or NLSVH, and admitted to the emergency department between July 2015 and October 2020 with a primary diagnosis of DKA and an elevated anion gap greater than or equal to 13 mEq/L.</p><p><strong>Results: </strong>A total of 90 patients from NLEMMC and 64 patients from NLSVH were included and compared to 111 patients from the University of Colorado who were included in the post protocol implementation group. There was no statistically significant difference in the primary outcome, time to anion gap closure, between the original University of Colorado study (10.3 hours) and the NLEMMC (10.9 hours, <i>p</i> = 0.420) and NLSVH (8.8 hours, <i>p</i> = 0.115) results presented in this study.</p><p><strong>Conclusion: </strong>The standardized nurse-driven DKA treatment protocol at NLEMMC and NLSVH showed no statistical difference in time to anion gap closure compared to the University of Colorado study upon which it was based. This finding is particularly relevant to hospitals such as NLEMMC and NLSVH that lack provider resources and teams of endocrinologists required for the physician-driven DKA protocol.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":" ","pages":"197-202"},"PeriodicalIF":2.0,"publicationDate":"2021-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/e7/cpaa-13-197.PMC8504870.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39540228","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}