{"title":"Evaluation of hepatic CYP2D1 activity and hepatic clearance in type I and type II diabetic rat models, before and after treatment with insulin and metformin.","authors":"Navid Neyshaburinezhad, Maryam Seidabadi, Mohammadreza Rouini, Hoda Lavasani, Alireza Foroumadi, Yalda H Ardakani","doi":"10.1007/s40199-020-00350-z","DOIUrl":"https://doi.org/10.1007/s40199-020-00350-z","url":null,"abstract":"<p><strong>Introduction: </strong>Conversion in the metabolism of drugs occurs in diabetes mellitus. Considering the importance of metabolic enzymes' activities on the efficacy and safety of medicines, the changes in liver enzymatic activity of CYP2D1 and its related hepatic clearance, by using Dextromethorphan as probe in the animal model of type I and type II diabetes, before and after treatment, was assessed in this study.</p><p><strong>Methods: </strong>Male Wistar rats were randomly divided into 6 groups. Seven days after induction of diabetes type I and type II, treatment groups were received insulin and metformin daily for 14 days, respectively. In day 21, rats were subjected to liver perfusion by Krebs-Henseleit buffer containing Dextromethorphan as CYP2D1 probe. Perfusate samples were analyzed by HPLC fluorescence method in order to evaluate any changes in CYP2D1 activity.</p><p><strong>Results: </strong>The average metabolic ratio of dextromethorphan and hepatic clearance were changed from 0.012 ± 0.004 and 6.3 ± 0.1 in the control group to 0.006 ± 0.0008 and 5.2 ± 0.2 in the untreated type I diabetic group, and 0.008 ± 0.003 and 5.0 ± 0.6 in the untreated type II diabetic rats. Finally, the mean metabolic ratio and hepatic clearance were changed to 0.008 ± 0.001 and 5.4 ± 0.1, and 0.013 ± 0.003 and 6.1 ± 0.4 in the treated groups with insulin and metformin, respectively.</p><p><strong>Conclusion: </strong>In type I diabetic rats, corresponding treatment could slightly improve enzyme activity, whereas the hepatic clearance and enzyme activity reached to the normal level in type II group. Graphical abstract .</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"28 2","pages":"479-487"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40199-020-00350-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37908759","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":"Factors affecting performance and manufacturability of naproxen Liqui-Pellet.","authors":"Matthew Lam, Ali Nokhodchi","doi":"10.1007/s40199-020-00362-9","DOIUrl":"https://doi.org/10.1007/s40199-020-00362-9","url":null,"abstract":"<p><strong>Aim: </strong>Liqui-Pellet is potentially an emerging next-generation oral pill, which has shown promising results with unique advantages as well as displaying potential for commercial feasibility. Since Liqui-Pellet technology is still in its infancy, it is important to explore the parameters that can affect its performance, particularly the drug release rate. Therefore, the aim of this study is to investigate thoroughly the effect of Avicel PH101 (carrier) and Aerosil 300 (coating material) ratio (R-value) in Liqui-Pellet.</p><p><strong>Methods: </strong>Key parameter for Liqui-Pellet formulation in this study was the ratio of carrier and coating material. Tests were carried out to assess the physicochemical properties of different formulations. This involved looking into particle size, robustness, flowability, solid-state and drug release profile. The morphology of Liqui-Pellet was investigated by SEM.</p><p><strong>Results: </strong>It is found that R-value does not have a major effect on the success of Liqui-Pellet production. However, R-value does seem to have an effect on Liqui-Pellet size at a certain water content level and a slight effect on the drug release rate. A decrease in Avicel PH101 concentration and an increase in Aerosil 300 concentration in Liqui-Pellet formulations can reduce Liqui-Pellet size and slightly increase drug release rate by 9% after 2 h. The data shows Liqui-Pellet is resistant to friability, able to achieve exceptional flow property and have smooth surfaces, which is critical for applying coatings technology. Such properties are ideal in terms of commercial manufacturing. The XRPD and DSC both show the reduction in formulation crystallinity, which is expected in Liqui-Pellet formulation as a result of solubility of the drug in the co-solvent used in the preparation of Liqui-Pellets.</p><p><strong>Conclusion: </strong>Overall it seems that R-value can affect Liqui-Pellet drug release rate and size but not on the production success rate.</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"28 2","pages":"567-579"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40199-020-00362-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38241100","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}
Daniela Calina, Thomas Hartung, Anca Oana Docea, Demetrios A Spandidos, Alex M Egorov, Michael I Shtilman, Felix Carvalho, Aristidis Tsatsakis
{"title":"COVID-19 vaccines: ethical framework concerning human challenge studies.","authors":"Daniela Calina, Thomas Hartung, Anca Oana Docea, Demetrios A Spandidos, Alex M Egorov, Michael I Shtilman, Felix Carvalho, Aristidis Tsatsakis","doi":"10.1007/s40199-020-00371-8","DOIUrl":"https://doi.org/10.1007/s40199-020-00371-8","url":null,"abstract":"<p><strong>Background: </strong>The pandemic associated with the new SARS-CoV-2 coronavirus continues to spread worldwide. The most favorable epidemic control scenario, which provides long-term protection against COVID-19 outbreak, is the development and distribution of an effective and safe vaccine. The need to develop a new COVID-19 vaccine is pressing; however, it is likely to take a long time, possibly several years. This is due to the time required to demonstrate the safety and efficacy of the proposed vaccine. and the time required to manufacture and distribute millions of doses.</p><p><strong>Objectives: </strong>To accelerate this development and associated safety testing, the deliberate infection of healthy volunteers has been suggested. The purpose of this short communication is to describe the ethical aspects of this type of testing, RESULTS: Deliberate infection of volunteers with a dangerous virus such as SARS-CoV-2 was initially considered unethical by researchers; but the current pandemic is so different from previous ones that these studies are considered ethical if certain criteria are met. Participants in human challenge studies must be relatively young, in good health and must receive the highest quality medical care, with frequent monitoring. Tests should also be performed with great caution and specialized medical supervision. Besides, the fact that obtaining vaccines faster through deliberate infection studies of healthy people has greater benefits than risks, has been demonstrated by obtaining other vaccines in other historical pandemics such as: smallpox, influenza, malaria, typhoid fever, Dengue fever and Zika.</p><p><strong>Conclusions: </strong>One possibility to shorten the time required for the development of COVID-19 vaccines is to reduce clinical phases II and III by using human challenge studies through eliberate infection of healthy volunteers with SARS-CoV-2 after administration of the candidate vaccine. Accelerating the development of a COVID-19 vaccine even for a few weeks or months would have a great beneficial impact on public health by saving many lives.</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"28 2","pages":"807-812"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40199-020-00371-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38314576","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":"Effect of a novel herbal vaginal suppository containing myrtle and oak gall in the treatment of vaginitis: a randomized clinical trial.","authors":"Sayyede Fatemeh Askari, Bahia Namavar Jahromi, Amirreza Dehghanian, Afsoon Zarei, Mojgan Tansaz, Parmis Badr, Amir Azadi, Abdolali Mohagheghzadeh","doi":"10.1007/s40199-020-00365-6","DOIUrl":"10.1007/s40199-020-00365-6","url":null,"abstract":"<p><strong>Background: </strong>Uncomplicated infections such as candidiasis, bacterial vaginosis (BV), or trichomoniasis are easy to diagnose and treat. However, about 8% of patients will have a more complicated course with failure to respond to treatment or rapid recurrence of symptoms. There are many suggestions in Traditional Persian Medicine like myrtle (Myrtus communis L.) and oak gall (Quercus infectoria G.Olivier) for treatment of vaginitis.</p><p><strong>Objectives: </strong>A clinical trial was designed to assess the efficacy of a novel herbal suppository, containing myrtle and oak gall (MOGS) in treatment of vaginitis.</p><p><strong>Methods: </strong>In a parallel randomized clinical trial, 120 women with vaginitis were randomly assigned to MOGS, metronidazole, or placebo. Formulation was simulated from traditional Persian manuscripts and MGOS was prepared after pharmaceutical optimization processing as well as quantification of gallic acid by HPLC. The study was double-blind for MOGS and placebo and single-blind for metronidazole group.</p><p><strong>Results: </strong>MOGS effectively improved vaginal discharge (p = 0.024 for BV and 0.018 for trichomoniasis) and pH (compared to placebo (p = 0.013) and metronidazole (p = 0.001)). Both MOGS and metronidazole could reverse whiff test. Metronidazole was the best medication for making Nugent score negative (p = 0.005) as well as the best therapy according to laboratory findings to treat BV in comparison with placebo (p = 0.021). While for trichomoniasis, MOGS could improve the disease more successfully (p = 0.001). Both MOGS and metronidazole treated mixed vaginitis (p = 0.002).</p><p><strong>Conclusion: </strong>MOGS would be a chance for developing new treatment for trichomoniasis.</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"28 2","pages":"603-614"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40199-020-00365-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38347078","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 outcomes of hospitalized patients with moderate and severe COVID-19 following treatment with hydroxychloroquine plus atazanavir/ritonavir.","authors":"Hamid Rahmani, Effat Davoudi-Monfared, Anahid Nourian, Morteza Nabiee, Setayesh Sadeghi, Hossein Khalili, Ladan Abbasian, Fereshteh Ghiasvand, Arash Seifi, Malihe Hasannezhad, Sara Ghaderkhani, Mostafa Mohammadi, Mir Saeed Yekaninejad","doi":"10.1007/s40199-020-00369-2","DOIUrl":"10.1007/s40199-020-00369-2","url":null,"abstract":"<p><strong>Background: </strong>The role of the antiviral therapy in treatment of COVID-19 is still a matter to be investigated. Also efficacy and safety of antiviral regimens were not compared according severity of the disease. In this study the efficacy and safety of hydroxychloroquine plus atazanavir/ritonavir was compared in patients with moderate and severe COVID-19.</p><p><strong>Methods: </strong>We prospectively evaluated the clinical outcomes of 213 patients with COVID-19 during the hospitalization course and up to 56 days after the hospital discharge. The disease was categorized to moderate and severe based on the severity of pneumonia and peripheral oxygen saturation (SpO2). The patients received the national treatment protocol containing hydroxychloroquine (400 mg BD in first day and then 200 mg BD) plus atazanavir/ritonavir (300/100 mg daily) for 7 days. Main outcomes included discharge rates at day 7, 14 and 28, 28-day mortality, rate of intensive care unit (ICU) admission and intubation, length of hospital and ICU stay and incidence of adverse events.</p><p><strong>Results: </strong>The mean (SD) age of patients was 60(14) years and 53% were male. According to WHO definition, 51.64% and 48.36% of the patients had moderate (SpO2 ≥ 90%) and severe disease (SpO2 < 90%) at baseline, respectively. The discharge rate of the moderate group was significantly higher than the severe group at day 7, 14 and 28 (HR = 0.49; 95% CI: 0.35-0.69, p = < 0.001 at day 7, HR = 0.48; 95% CI: 0.35-0.66, p = < 0.001 at day 14 and HR = 0.49; 95% CI: 0.36-0.67, p = < 0.001at day 28). The 28-day mortality of the severe group was six times higher than the moderate group (HR = 6.00; 95% CI: 2.50-14.44), p = < 0.001). The need of admission in ICU for the severe group and the moderate group was 37.86% and 18.18% of the patients. Length of hospital stay was significantly shorter in the moderate group in comparison with the severe group (5 ± 4 vs. 8 ± 6 days, p < 0.001). Patients in the moderate group experienced the serious adverse events and complications less than the severe group. The discharged patients were followed up to 56 days after discharge. Some of the patients complained of symptoms such as exertional dyspnea, weakness and new-onset hair loss.</p><p><strong>Conclusion: </strong>Our study did not support the use of hydroxychloroquine plus atazanavir/ritonavir in patients who had SpO<sub>2</sub> < 90% at the time of hospital admission. SpO2 was the only predictor of clinical outcomes (duration of hospital stay, discharge from the hospital and mortality) in patients treated with hydroxychloroquine plus atazanavir/ritonavir.</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"28 2","pages":"625-634"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38319918","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}
Surya P Singh, Sanjay Kumar, Sivapar V Mathan, Munendra Singh Tomar, Rishi Kant Singh, Praveen Kumar Verma, Amit Kumar, Sandeep Kumar, Rana P Singh, Arbind Acharya
{"title":"Therapeutic application of Carica papaya leaf extract in the management of human diseases.","authors":"Surya P Singh, Sanjay Kumar, Sivapar V Mathan, Munendra Singh Tomar, Rishi Kant Singh, Praveen Kumar Verma, Amit Kumar, Sandeep Kumar, Rana P Singh, Arbind Acharya","doi":"10.1007/s40199-020-00348-7","DOIUrl":"10.1007/s40199-020-00348-7","url":null,"abstract":"<p><strong>Introduction: </strong>Papaya (Carica papaya Linn.) belongs to the family Caricaceae and is well known for its therapeutic and nutritional properties all over the world. The different parts of the papaya plant have been used since ancient times for its therapeutic applications. Herein, we aimed to review the anticancer, anti-inflammatory, antidiabetic and antiviral activities of papaya leaf.</p><p><strong>Methods: </strong>All information presented in this review article regarding the therapeutic application of Carica papaya leaf extract has been acquired by approaching various electronic databases, including Scopus, Google scholar, Web of science, and PubMed. The keywords Carica papaya, anticancer, anti-inflammatory, immunomodulatory, and phytochemicals were explored until December 2019.</p><p><strong>Results: </strong>The papaya plant, including fruit, leaf, seed, bark, latex, and their ingredients play a major role in the management of disease progression. Carica papaya leaf contains active components such as alkaloids, glycosides, tannins, saponins, and flavonoids, which are responsible for its medicinal activity. Additionally, the leaf juice of papaya increases the platelet counts in people suffering from dengue fever.</p><p><strong>Conclusion: </strong>The major findings revealed that papaya leaf extract has strong medicinal properties such as antibacterial, antiviral, antitumor, hypoglycaemic and anti-inflammatory activity. Furthermore, clinical trials are needed to explore the medicative potential of papaya leaf. Graphical abstract Graphical abstract showing the medicinal properties of Carica papaya leaf.</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"28 2","pages":"735-744"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40199-020-00348-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37899350","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":"COVID-19 and off label use of drugs: an ethical viewpoint.","authors":"Amirahmad Shojaei, Pooneh Salari","doi":"10.1007/s40199-020-00351-y","DOIUrl":"https://doi.org/10.1007/s40199-020-00351-y","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 outbreak is rapidly spread over the world and kills infected patients. There is no proven medication for its treatment, so, all of the medications used for treatment are considered to be off-label. Off-label uses are not under regulation in the outbreak because there is no specific regulation for this condition.</p><p><strong>Objectives: </strong>In this short communication we aim at describing two ways of off-label use as clinical practice or investigational use. Further, we will describe the third way of off-label use, we named it pseudo-research and then we will state the most possible ethical challenges of off-label use for better perceptions and responsibility.</p><p><strong>Results: </strong>The WHO considers off-label uses as country-specific. All international regulatory bodies consider off-label prescription as the physician's responsibility and legal by necessitating some requirements. There is no international guideline for regulating investigational off-label uses as clinical practice.</p><p><strong>Conclusion: </strong>There are different types of approaches, none of them is comprehensive and conclusive. Furthermore, respecting the four ethical principles necessitates codification and strict regulation of off-label uses either as clinical practice or investigational. Besides, compilation of a special guideline based on ethical principles especially non-maleficence and autonomy for investigational off-label uses in disasters is highly recommended.</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"28 2","pages":"789-793"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40199-020-00351-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37915947","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":"Bibenzyls and bisbybenzyls of bryophytic origin as promising source of novel therapeutics: pharmacology, synthesis and structure-activity.","authors":"Samapika Nandy, Abhijit Dey","doi":"10.1007/s40199-020-00341-0","DOIUrl":"10.1007/s40199-020-00341-0","url":null,"abstract":"<p><strong>Background: </strong>The amphibian, non-vascular, gametophyte-dominant, bio-indicator class, bryophytes; with their wide ranges of habitat have attained importance due to their promising medicinal attributions and therapeutic role; mostly aided by presence of aromatic bibenzyl and bisbybenzyl class of compounds. Bibenzyls are steroidal ethane derivatives, resembling the structural moiety of bioactive dihydro-stilbenoids or iso-quinoline alkaloids. These stress triggered secondary metabolites are the by-products of the flavonoid biosynthetic pathway. Different classes of bryophytes (Bryophyta, Marchantiophyta and Anthocerotophyta) possess different subtypes of bibenzyls and dimeric bisbibenzyls. Among the liverwort, hornwort and mosses, former one is mostly enriched with bibenzyl type constituents as per the extensive study conducted for phytochemical deposit. Considering macrocyclic and acyclic group of bibenzyls and bisbybenzyls, generally marchantin type compounds are reported vividly for significant biological activity that includes neuro-nephro-cardio-protection besides anti-allergic, anti-microbial, anti-apoptotic and cytotoxic activities studied on in-vitro and in-vivo models or on cell lines.</p><p><strong>Result: </strong>The critical analysis of reported chemical and pharmaceutical attributions of bibenzyls and bis-bibenzyls yielded detailed report on this compound class along with their application, mode of action, natural source, techniques of synthesis, extraction procedure, isolation and characterization. Further, the structure activity relationship studies and bioactivity of bibenzyls derived from non-bryophytic origin were also summarized.</p><p><strong>Conclusion: </strong>This review encompasses prospective biological application of botanical reservoir of this primarily ignored, primeval land plant group where recent technical advances has paved the way for qualitative and quantitative isolation and estimation of novel compounds as well as marker components to study their impact on environment, as bio-control agents and as key leads in future drug designing. Graphical abstract.</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"28 2","pages":"701-734"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40199-020-00341-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38270498","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}
Behrouz Seyfinejad, Maryam Khoubnasabjafari, Saba Eivaz Ziaei, Sibel A Ozkan, Abolghasem Jouyban
{"title":"Electromembrane extraction as a new approach for determination of free concentration of phenytoin in plasma using capillary electrophoresis.","authors":"Behrouz Seyfinejad, Maryam Khoubnasabjafari, Saba Eivaz Ziaei, Sibel A Ozkan, Abolghasem Jouyban","doi":"10.1007/s40199-020-00366-5","DOIUrl":"https://doi.org/10.1007/s40199-020-00366-5","url":null,"abstract":"<p><strong>Purpose: </strong>Electromembrane extraction is a new membrane-based extraction method in which charged compounds are extracted by an electric field. So far, this method has been used to extract and isolate a variety of acidic and basic drugs from various samples, including blood and plasma. However, in this procedure, it is not yet clear whether only unbound fraction of a drug is extracted or the total drug. The aim of this study is to reveal the nature of drug extraction in the presence of plasma proteins.</p><p><strong>Methods: </strong>To determine the nature of the extraction, the electromembrane extraction was performed from plasma solutions of phenytoin with concentrations 0.03 and 1.0 μg/mL, then the result was compared with the values obtained from the electromembrane extraction of ultrafiltrate of the same solutions (free concentration) and protein-free ultrafiltrate of plasma with final concentration of 0.03 and 1.0 μg/mL (total concentration). For this purpose, EME followed by capillary electrophoresis coupled with diode array detection was optimized and validated.</p><p><strong>Results: </strong>The results showed that the electromembrane extraction method was only able to extract the unbound fraction of phenytoin from plasma samples. The method was validated over a concentration range of 0.03-4 μg/mL. The inter and intra-assay precisions were less than 6.7%. The phenytoin protein binding was also determined to be in agreement with the literature data and confirms the validity of this method.</p><p><strong>Conclusion: </strong>This sensitive and quick EME approach for determining the free concentration of a phenytoin, can be a good alternative to classic methods for therapeutic drug monitoring and pharmacokinetic studies.</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"28 2","pages":"615-624"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40199-020-00366-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38270499","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":"Classification of the present pharmaceutical agents based on the possible effective mechanism on the COVID-19 infection.","authors":"Maryam Amini Pouya, Seyyedeh Maryam Afshani, Armin Salek Maghsoudi, Shokoufeh Hassani, Kayvan Mirnia","doi":"10.1007/s40199-020-00359-4","DOIUrl":"10.1007/s40199-020-00359-4","url":null,"abstract":"<p><strong>Objectives: </strong>There are several types of research on the COVID-19 disease which have been conducting. It seems that prevailing over the pandemic would be achieved only by mastering over the virus pathophysiology. We tried to categorize the massive amount of available information for useful interpretation.</p><p><strong>Evidence acquisition: </strong>We searched databases with different keywords and search strategies that focus on virulence and pathophysiology of COVID-19. The present review has aimed to gather and categorize all implemented drugs based on the susceptible virulence mechanisms, and the pathophysiological events in the host cells, discussing and suggesting treatments.</p><p><strong>Results: </strong>As a result, the COVID-19 lifecycle were categorized as following steps: \"Host Cell Attachment\" which is mainly conducted with ACE<sub>2</sub> receptors and TMPRSS2 from the host cell and Spike (S) protein, \"Endocytosis Pathway\" which is performed mainly by clathrin-mediated endocytosis, and \"Viral Replication\" which contains translation and replication of RNA viral genome. The virus pathogenicity is continued by \"Inflammatory Reactions\" which mainly caused moderate to severe COVID-19 disease. Besides, the possible effective therapeutics' mechanism and the pharmaceutical agents that had at least one experience as a preclinical or clinical study on COVID-19 were clearly defined.</p><p><strong>Conclusion: </strong>The treatment protocol would be occasional based on the stage of the infection and the patient situation. The cocktail of medicines, which could affect almost all mentioned stages of COVID-19 disease, might be vital for patients with severe phenomena. The classification of the possible mechanism of medicines based on COVID-19 pathogenicity.</p>","PeriodicalId":10961,"journal":{"name":"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences","volume":"28 2","pages":"745-764"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40199-020-00359-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38214353","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}