{"title":"DPP4 Inhibitors: Could they be One of the Solutions for COVID-19 Patients with Prediabetes?","authors":"Ntethelelo Hopewell Sibiya, Bongeka Cassandra Mkhize, Andile Khathi","doi":"10.2174/2772432817666220127163457","DOIUrl":"https://doi.org/10.2174/2772432817666220127163457","url":null,"abstract":"<p><p>Recent reports suggest that prediabetes is a risk factor for developing severe COVID-19 complications through underlying mechanisms involving undiagnosed sub-clinical inflammation. However, we remain without a clinical approach for managing COVID-19 in prediabetic cases. The subclinical inflammation in prediabetes is associated with elevated DPP4 levels and activity. DPP4 has pleiotropic actions, including glycaemia regulation and immuno-modulation. Recently, DPP4 has been recognised as a co-receptor for COVID-19 for entering host cells. In addition to improving glycaemia, DPP4 inhibition is associated with reduced inflammation. In this submission, we explore the potential use of DPP4 inhibitors as therapeutic agents for prediabetic patients in managing the deleterious effects of COVID-19. DPP4 inhibitors (gliptins), such as linagliptin and sitagliptin, have therapeutic effects, which have been shown to extend beyond glycaemic control with no risk of hypoglycaemia. By the nature of their mechanism of action, gliptins are not associated with hypoglycaemia, unlike their anti-glycaemic counterparts, as they mainly target postprandial glycaemia. Moreover, DPP4 inhibitors may represent a safer option for prediabetic individuals in managing prediabetes either as a prophylactic or curative treatment for COVID-19. We envisage that beyond improved glycaemic control, the use of DPP4 inhibitors would also alleviate the cytokine storm, resulting in a reduction in the severity of COVID-19 symptoms and consequently reducing the morbidity and mortality in prediabetic COVID- 19 patients.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"18 1","pages":"88-91"},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9536588","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 Status of Pharmacokinetic Research in Children: A Systematic Review of Clinical Trial Records.","authors":"Pugazhenthan Thangaraju, Hemasri Velmurugan, Krishnapriya Neelambaran","doi":"10.2174/2772432818666221223155455","DOIUrl":"10.2174/2772432818666221223155455","url":null,"abstract":"<p><strong>Background: </strong>Many medications have different pharmacokinetics in children than in adults. Knowledge about the safety and efficacy of medications in children requires research into the pharmacokinetic profiles of children's medicines. By analysing registered clinical trial records, this study determined how frequently pharmacokinetic data is gathered in paediatric drug trials.</p><p><strong>Methods: </strong>We searched for the pharmacokinetic data from clinical trial records for preterm infants and children up to the age of 16 from January 2011 to April 2022. The records of trials involving one or more drugs in preterm infants and children up to the age of 16 were examined for evidence that pharmacokinetic data would be collected.</p><p><strong>Results: </strong>In a total of 1483 records of interventional clinical trials, 136 (9.17%) pharmacokinetic data involved adults. Of those 136 records, 60 (44.1%) records were pharmacokinetics trials involving one or more medicines in children up to the age of 16.20 (33.3%) in America, followed by 19 (31.6%) in Europe. Most trials researched medicines in the field of infection or parasitic diseases 20 (33.3%). 27 (48.2%) and 26 (46.4%) trials investigated medicines that were indicated as essential medicine.</p><p><strong>Conclusion: </strong>The pharmacokinetic characteristics of children's drugs need to be better understood. The current state of pharmacokinetic research appears to address the knowledge gap in this area adequately. Despite slow progress, paediatric clinical trials have experienced a renaissance as the significance of paediatric trials has gained international attention. The outcome of paediatric trials will have an impact on children's health in the future. In recent years, the need for greater availability and access to safe child-size pharmaceuticals has received a lot of attention.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"78-92"},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10445313","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":"Antibiotics with Antiviral and Anti-Inflammatory Potential Against Covid-19: A Review.","authors":"Banafshe Abadi, Mehran Ilaghi, Yasamin Shahsavani, Mahsa Faramarzpour, Mohammad Bagher Oghazian, Hamid-Reza Rahimi","doi":"10.2174/2772432817666220106162013","DOIUrl":"https://doi.org/10.2174/2772432817666220106162013","url":null,"abstract":"<p><p>In Covid-19 cases, elderly patients in long-term care facilities, children younger than five years with moderate symptoms, and patients admitted to ICU or with comorbidities are at a high risk of coinfection, as suggested by the evidence. Thus, in these patients, antibiotic therapy based on empirical evidence is necessary. Finding appropriate antimicrobial agents, especially with antiviral and anti-inflammatory properties, is a promising approach to target the virus and its complications, hyper-inflammation, and microorganisms resulting in co-infection. Moreover, indiscriminate use of antibiotics can be accompanied by Clostridioides difficile colitis, the emergence of resistant microorganisms, and adverse drug reactions, particularly kidney damage and QT prolongation. Therefore, rational administration of efficient antibiotics is an important issue. The main objective of the present review is to provide a summary of antibiotics with possible antiviral activity against SARS-CoV-2 and anti-immunomodulatory effects to guide scientists for further research. Besides, the findings can help health professionals in the rational prescription of antibiotics in Covid-19 patients with a high risk of co-infection.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"18 1","pages":"51-63"},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9169125","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 Trends in the Animal Models for Screening of Nootropic Agents: A Systematic Review.","authors":"Shubhima Grover, Seema Jain","doi":"10.2174/2772432817666220425121323","DOIUrl":"https://doi.org/10.2174/2772432817666220425121323","url":null,"abstract":"<p><strong>Background: </strong>Deficits in cognitive functions are observed in various diseases. The term \"nootropics\" refers to the compounds that increase mental functions, including memory, motivation, concentration and attention. Given the complexity and vastness of the processes involved in cognition, developing an appropriate animal model for the screening of nootropic agents still remains a daunting task.</p><p><strong>Objectives: </strong>This review attempts to elicit the current trends in the animal models being used for screening of nootropic agents and effectively use this knowledge to improve prospects embarking on this area of research.</p><p><strong>Methods: </strong>Electronic searches were carried out on PubMed using the keywords \"nootropic agents\"[MeSH Term] OR \"nootropic drugs\" [MeSH Term] AND \"animal model\" [MeSH Term] OR \"animal model, experimental\" [MeSH Term]. All relevant studies from 2016 to 31st August, 2021, were then reviewed to meet the stated objective.</p><p><strong>Results: </strong>The most commonly used disease model for screening of nootropic agents was found to be the animal model of Alzheimer's disease. Disease models of vascular dementia or stroke, depression or anxiety, schizophrenia, epilepsy or seizure, diabetes and traumatic brain injury, among others, have also been used. There exists a wide variety of behavioral tests to assess cognition.</p><p><strong>Conclusion: </strong>Since a variety of etiologies can affect cognitive processes. Hence, a nootropic agent may be screened in a variety of disease models. The most widely used and appropriate method to assess cognition would be by combining the behavioral and biochemical assays so that a more comprehensive profile of the nootropic effects of a drug can be elicited.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"18 3","pages":"255-269"},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9169147","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":"Comparison of Aspirin and P2Y<sub>12</sub> Inhibitors for Secondary Prevention of Ischaemic Stroke: A Systematic Review and Meta-analysis.","authors":"Kaili Zhang, Yongle Wang, Tingting Liu, Xiaoyuan Niu","doi":"10.2174/2772432817666220526162144","DOIUrl":"https://doi.org/10.2174/2772432817666220526162144","url":null,"abstract":"<p><strong>Background: </strong>P2Y<sub>12</sub> inhibitors have been widely used as an alternative to aspirin in clinical practice for secondary stroke prevention. We aimed to compare the efficiency and safety of P2Y<sub>12</sub> inhibitors and aspirin for stroke prevention in patients with previous stroke or transient ischaemic attack (TIA).</p><p><strong>Methods: </strong>PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. All randomized trials that compared P2Y<sub>12</sub> inhibitors with aspirin among patients with stroke were included. The primary efficacy outcomes of our meta-analysis included stroke, vascular events, and all-cause death. The primary safety outcome was minor or major bleeding events.</p><p><strong>Results: </strong>The search identified 4 randomized clinical trials comparing P2Y<sub>12</sub> inhibitors with aspirin for secondary stroke prevention that collectively enrolled 24508 patients (12253 received P2Y<sub>12</sub> inhibitor and 12255 received aspirin). Pooled results from the random-effects model showed that there were no significant differences in the risk of any stroke (OR 0.90 (0.78-1.04); I²=56.9%), vascular event (OR 0.91 (0.74-1.13); I²=78.3%), all-cause death (OR 0.98 (0.83-1.17); I²=0%), or minor or major bleeding (OR 1.13 (0.70-1.82); I²=79%) among patients who received a P2Y<sub>12</sub> inhibitor or aspirin. P2Y<sub>12</sub> inhibitors were associated with a significantly lower risk of recurrent ischaemic stroke (OR 0.84 (0.73- 0.96); I²=25%) than aspirin.</p><p><strong>Conclusion: </strong>This meta-analysis suggests that P2Y<sub>12</sub> inhibitors are more effective than aspirin in preventing recurrent ischaemic stroke among ischaemic stroke patients despite the absence of any effect on a new ischaemic or haemorrhagic stroke, a new clinical vascular event, all-cause death, and major or minor bleeding events.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"18 3","pages":"270-283"},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9169861","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":"Preface","authors":"A. Mangoni","doi":"10.2174/277243281801221110142524","DOIUrl":"https://doi.org/10.2174/277243281801221110142524","url":null,"abstract":"","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45296089","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":"Special issue: Innovations in Early Clinical Drug Evaluation.","authors":"E. Hoogdalem, G. Bernstein","doi":"10.2174/277243281701211223102125","DOIUrl":"https://doi.org/10.2174/277243281701211223102125","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"17 1 1","pages":"3"},"PeriodicalIF":1.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43402886","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":"Patient-Centricity: A Much-Needed Strategy to Enhance the Quality Use of Medicines in Older Patients.","authors":"A. Mangoni, E. Jarmuzewska","doi":"10.2174/277243281701211223100004","DOIUrl":"https://doi.org/10.2174/277243281701211223100004","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"17 1 1","pages":"1-2"},"PeriodicalIF":1.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49102252","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}
Ad Roffel, Jan Jaap van Lier, Gerk Rozema, Ewoud-Jan van Hoogdalem
{"title":"Predictability of Elimination and Excretion of Small Molecules in Animals and Humans, and its Impact on Dosimetry for human ADME Studies with Radiolabeled Drugs.","authors":"Ad Roffel, Jan Jaap van Lier, Gerk Rozema, Ewoud-Jan van Hoogdalem","doi":"10.2174/1574884716666210309103625","DOIUrl":"https://doi.org/10.2174/1574884716666210309103625","url":null,"abstract":"<p><strong>Background: </strong>We assessed the extent to which urinary and fecal excretion of <i>14</i>C-labeled drug material in animal ADME studies was predictive of human ADME studies. We compared observed plasma elimination half-lives for total drug-related radioactivity in humans to pre-study predictions, and we estimated the impact of any major differences on human dosimetry calculations.</p><p><strong>Methods: </strong>We included 34 human ADME studies with doses of <i>14</i>C above 0.1 MBq. We calculated ratios of dosimetry input parameters (percentage fecal excretion in humans <i>versus</i> animals; observed half-life in humans <i>versus</i> predicted pre-study) and output parameters (effective dose post-study <i>versus</i> pre-study) and assessed their relationship.</p><p><strong>Results: </strong>A quantitative correlation assessment did not show a statistically significant correlation between the ratios of percentages of <i>14</i>C excreted in feces and the ratios of dosimetry outcomes in the entire dataset, but a statistically significant correlation was found when assessing the studies that were based on ICRP 60/62 (n=19 studies; P=0.0028). There also appeared to be a correlation between the plasma half-life ratios and the ratios of dosimetry results. A quantitative correlation assessment showed that there was a statistically significant correlation between these ratios (P<0.0001).</p><p><strong>Conclusion: </strong>In all cases where the plasma elimination half-life for <i>14</i>C in humans was found to be longer than the predicted value, the radiation burden was still within ICRP Category IIa. Containment of the actual radiation burden below the limit of 1.00 mSv appeared to be determined partly also by our choice to limit <i>14</i>C doses to 3.7 MBq.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"17 1","pages":"26-38"},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25466873","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}