Drug Metabolism Reviews最新文献

{"title":"Ibuprofen-based advanced therapeutics: breaking the inflammatory link in cancer, neurodegeneration, and diseases.","authors":"Arun Upadhyay,&nbsp;Ayeman Amanullah,&nbsp;Vibhuti Joshi,&nbsp;Rohan Dhiman,&nbsp;Vijay Kumar Prajapati,&nbsp;Krishna Mohan Poluri,&nbsp;Amit Mishra","doi":"10.1080/03602532.2021.1903488","DOIUrl":"https://doi.org/10.1080/03602532.2021.1903488","url":null,"abstract":"<p><p>Ibuprofen is a classical nonsteroidal anti-inflammatory drug (NSAID) highly prescribed to reduce acute pain and inflammation under an array of conditions, including rheumatoid arthritis, osteoarthritis, dysmenorrhea, and gout. Ibuprofen acts as a potential inhibitor for cyclooxygenase enzymes (COX-1 and COX-2). In the past few decades, research on this small molecule has led to identifying other possible therapeutic benefits. Anti-tumorigenic and neuroprotective functions of Ibuprofen are majorly recognized in recent literature and need further consideration. Additionally, several other roles of this anti-inflammatory molecule have been discovered and subjected to experimental assessment in various diseases. However, the major challenge faced by Ibuprofen and other drugs of similar classes is their side effects, and tendency to cause gastrointestinal injury, generate cardiovascular risks, modulate hepatic and acute kidney diseases. Future research should also be conducted to deduce new methods and approaches of suppressing the unwanted toxic changes mediated by these drugs and develop new therapeutic avenues so that these small molecules continue to serve the purposes. This article primarily aims to develop a comprehensive and better understanding of Ibuprofen, its pharmacological features, therapeutic benefits, and possible but less understood medicinal properties apart from major challenges in its future application.KEY POINTSIbuprofen, an NSAID, is a classical anti-inflammatory therapeutic agent.Pro-apoptotic roles of NSAIDs have been explored in detail in the past, holding the key in anti-cancer therapies.Excessive and continuous use of NSAIDs may have several side effects and multiple organ damage.Hyperactivated Inflammation initiates multifold detrimental changes in multiple pathological conditions.Targeting inflammatory pathways hold the key to several therapeutic strategies against many diseases, including cancer, microbial infections, multiple sclerosis, and many other brain diseases.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 1","pages":"100-121"},"PeriodicalIF":5.9,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2021.1903488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25562879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular modeling approaches to address drug-metabolizing enzymes (DMEs) mediated chemoresistance: a review.","authors":"Baddipadige Raju,&nbsp;Shalki Choudhary,&nbsp;Gera Narendra,&nbsp;Himanshu Verma,&nbsp;Om Silakari","doi":"10.1080/03602532.2021.1874406","DOIUrl":"https://doi.org/10.1080/03602532.2021.1874406","url":null,"abstract":"<p><p>Resistance against clinically approved anticancer drugs is the main roadblock in cancer treatment. Drug metabolizing enzymes (DMEs) that are capable of metabolizing a variety of xenobiotic get overexpressed in malignant cells, therefore, catalyzing drug inactivation. As evident from the literature reports, the levels of DMEs increase in cancer cells that ultimately lead to drug inactivation followed by drug resistance. To puzzle out this issue, several strategies inclusive of analog designing, prodrug designing, and inhibitor designing have been forged. On that front, the implementation of computational tools can be considered a fascinating approach to address the problem of chemoresistance. Various research groups have adopted different molecular modeling tools for the investigation of DMEs mediated toxicity problems. However, the utilization of these <i>in-silico</i> tools in maneuvering the DME mediated chemoresistance is least considered and yet to be explored. These tools can be employed in the designing of such chemotherapeutic agents that are devoid of the resistance problem. The current review canvasses various molecular modeling approaches that can be implemented to address this issue. Special focus was laid on the development of specific inhibitors of DMEs. Additionally, the strategies to bypass the DMEs mediated drug metabolism were also contemplated in this report that includes analogs and pro-drugs designing. Different strategies discussed in the review will be beneficial in designing novel chemotherapeutic agents that depreciate the resistance problem.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 1","pages":"45-75"},"PeriodicalIF":5.9,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2021.1874406","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25327681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What dominates the changeable pharmacokinetics of natural sesquiterpene lactones and diterpene lactones: a review focusing on absorption and metabolism.","authors":"Ziwei Yu,&nbsp;Ziqiang Chen,&nbsp;Qijuan Li,&nbsp;Ke Yang,&nbsp;Zecheng Huang,&nbsp;Wenjun Wang,&nbsp;Siyu Zhao,&nbsp;Huiling Hu","doi":"10.1080/03602532.2020.1853151","DOIUrl":"https://doi.org/10.1080/03602532.2020.1853151","url":null,"abstract":"<p><p>Sesquiterpene lactones (STLs) and diterpene lactones (DTLs) are two groups of common phytochemicals with similar structures. It's frequently reported that both exhibit changeable pharmacokinetics (PK) <i>in vivo</i>, especially the unstable absorption and extensive metabolism. However, the recognition of their PK characteristics is still scattered. In this review, representative STLs (atractylenolides, alantolactone, costunolide, artemisinin, etc.) and DTLs (ginkgolides, andrographolide, diosbulbins, triptolide, etc.) as typical cases are discussed in detail. We show how the differences of treatment regimens and subjects alter the PK of STLs and DTLs, with emphasis on the effects from absorption and metabolism. These compounds tend to be quite permeable in intestinal epithelium, but gastrointestinal pH and efflux transporters (represented by P-glycoprotein) have great impact and result in the unstable absorption. As the only characteristic functional moiety, the metabolic behavior of lactone ring is not dominant. The α, β-unsaturated lactone moiety has the strongest metabolic activity. While with the increase of low-activity saturated lactone moieties, the metabolism is led by other groups more easily. The phase I (oxidation, reduction and hydrolysis reaction) and II metabolism (conjugation reaction) are both extensive. CYP450s, mainly CYP3A4, are largely involved in biotransformation. However, only UGTs (UGT1A3, UGT1A4, UGT2B4 and UGT2B7) has been mentioned in studies about phase II metabolic enzymes. Our work offers a beneficial reference for promoting the safety evaluation and maximizing the utilization of STLs and DTLs.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 1","pages":"122-140"},"PeriodicalIF":5.9,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2020.1853151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38619698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent biotechnological approaches for treatment of novel COVID-19: from bench to clinical trial.","authors":"Seyyed Mojtaba Mousavi,&nbsp;Seyyed Alireza Hashemi,&nbsp;Najmeh Parvin,&nbsp;Ahmad Gholami,&nbsp;Seeram Ramakrishna,&nbsp;Navid Omidifar,&nbsp;Mohsen Moghadami,&nbsp;Wei-Hung Chiang,&nbsp;Sargol Mazraedoost","doi":"10.1080/03602532.2020.1845201","DOIUrl":"https://doi.org/10.1080/03602532.2020.1845201","url":null,"abstract":"<p><p>The global spread of the novel coronavirus (SARS-CoV-2) and increasing rate of mortality among different countries has raised the global concern regarding this disease. This illness is able to infect human beings through person-to-person contact at an extremely high rate. World Health Organization proclaimed that COVID-19 disease is known as the sixth public health emergency of international concern (30 January 2020) and also as one pandemic (12 March 2020). Owing to the rapid outbreak of COVID-19 worldwide, health authorities focused on discovery of effective prevention and treatment techniques for this novel virus. To date, an effective drug for reliable treatment of COVID-19 has not been registered or introduced to the international community. This review aims to provide recently presented techniques and protocols for efficient treatment of COVID-19 and investigate its morphology and treatment/prevention approaches, among which usage of antiviral drugs, anti-malarial drugs, corticosteroids, and traditional medicines, biotechnological drugs (e.g. combination of HCQ and azithromycin, remdesivir, interferons, novaferon, interferon-alpha-1b, thymosin, and monoclonal antibodies) can be mentioned.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 1","pages":"141-170"},"PeriodicalIF":5.9,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2020.1845201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38654130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moonlighting in drug metabolism.","authors":"Philip G Board,&nbsp;M W Anders","doi":"10.1080/03602532.2020.1858857","DOIUrl":"https://doi.org/10.1080/03602532.2020.1858857","url":null,"abstract":"<p><p>Drug metabolizing enzymes catalyze the biotransformation of many of drugs and chemicals. The drug metabolizing enzymes are distributed among several evolutionary families and catalyze a range of detoxication reactions, including oxidation/reduction, conjugative, and hydrolytic reactions that serve to detoxify potentially toxic compounds. This detoxication function requires that drug metabolizing enzymes exhibit substrate promiscuity. In addition to their catalytic functions, many drug metabolizing enzymes possess functions unrelated to or in addition to catalysis. Such proteins are termed 'moonlighting proteins' and are defined as proteins with multiple biochemical or biophysical functions that reside in a single protein. This review discusses the diverse moonlighting functions of drug metabolizing enzymes and the roles they play in physiological functions relating to reproduction, vision, cell signaling, cancer, and transport. Further research will likely reveal new examples of moonlighting functions of drug metabolizing enzymes.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 1","pages":"76-99"},"PeriodicalIF":5.9,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2020.1858857","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38667022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYP1A2 and tobacco interaction: a major pharmacokinetic challenge during smoking cessation.","authors":"Malcolm Barrangou-Poueys-Darlas, Marylène Guerlais, Edouard-Jules Laforgue, Ronan Bellouard, Marion Istvan, Pascale Chauvin, Jean-Yves Guillet, Pascale Jolliet, Matthieu Gregoire, Caroline Victorri-Vigneau","doi":"10.1080/03602532.2020.1859528","DOIUrl":"10.1080/03602532.2020.1859528","url":null,"abstract":"<p><p>Smoking cessation is underestimated in terms of drug interactions. Abrupt smoking cessation is common in cases of emergency hospitalization and restrictions of movement. Tobacco is a known cytochrome P450 1A2 (CYP1A2) inducer, its consumption and withdrawal can lead to major pharmacokinetic drug interactions. Nevertheless, references do exist, but may have different results between them. The objective of our work was to establish the broadest and most consensual list as possible of CYP1A2 substrates treatments and propose a pharmacological approach. We searched the widest possible list of CYP1A2 substrates based on various international references. We compared the references and defined probability and reliability scores of our results to sort the substances based on the scores. For the 245 substances identified as CYP1A2 substrates, we focused on the 63 CYP1A2 substrates with both probability and reliability scores >50%. Our work establishes adaptive pharmacological approaches for the management of patients initiating smoking cessation which must be integrated into the management of smoking cessation. Pharmacologists can now adopt adaptive pharmacological approaches to complement patient-specific clinical information about smoking cessation by considering pharmacokinetic risk. This work establishes an unprecedented list. It should guide in the care of patients initiating smoking cessation to prevent pharmacokinetic drug interactions.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 1","pages":"30-44"},"PeriodicalIF":3.4,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38715060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/03602532.2021.1907078","DOIUrl":"https://doi.org/10.1080/03602532.2021.1907078","url":null,"abstract":"","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 1","pages":"I-VI"},"PeriodicalIF":5.9,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2021.1907078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25528218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytochrome P450 expression and regulation in the brain.","authors":"Wojciech Kuban,&nbsp;Władysława Anna Daniel","doi":"10.1080/03602532.2020.1858856","DOIUrl":"https://doi.org/10.1080/03602532.2020.1858856","url":null,"abstract":"<p><p>The regulation of brain cytochrome P450 enzymes (CYPs) is different compared with respective hepatic enzymes. This may result from anatomical bases and physiological functions of the two organs. The brain is composed of a variety of functional structures built of different interconnected cell types endowed with specific receptors that receive various neuronal signals from other brain regions. Those signals activate transcription factors or alter functioning of enzyme proteins. Moreover, the blood-brain barrier (BBB) does not allow free penetration of all substances from the periphery into the brain. Differences in neurotransmitter signaling, availability to endogenous and exogenous active substances, and levels of transcription factors between neuronal and hepatic cells lead to differentiated expression and susceptibility to the regulation of <i>CYP</i> genes in the brain and liver. Herein, we briefly describe the CYP enzymes of CYP1-3 families, their distribution in the brain, and discuss brain-specific regulation of <i>CYP</i> genes. In parallel, a comparison to liver <i>CYP</i> regulation is presented. CYP enzymes play an essential role in maintaining the levels of bioactive molecules within normal ranges. These enzymes modulate the metabolism of endogenous neurochemicals, such as neurosteroids, dopamine, serotonin, melatonin, anandamide, and exogenous substances, including psychotropics, drugs of abuse, neurotoxins, and carcinogens. The role of these enzymes is not restricted to xenobiotic-induced neurotoxicity, but they are also involved in brain physiology. Therefore, it is crucial to recognize the function and regulation of CYP enzymes in the brain to build a foundation for future medicine and neuroprotection and for personalized treatment of brain diseases.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"53 1","pages":"1-29"},"PeriodicalIF":5.9,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2020.1858856","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38746283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Dioscorea bulbifera</i> L.-induced hepatotoxicity and involvement of metabolic activation of furanoterpenoids.","authors":"Hui Li,&nbsp;Ying Peng,&nbsp;Jiang Zheng","doi":"10.1080/03602532.2020.1800724","DOIUrl":"https://doi.org/10.1080/03602532.2020.1800724","url":null,"abstract":"<p><p>The rhizome of <i>Dioscorea bulbifera</i> L. (DBL) is a popular traditional herb in the treatment of goiters, breast lumps, and tumors. Unfortunately, DBL can give rise to severe hepatotoxicity. More than 100 cases of liver injury, due to the usage of DBL in China, have been reported in the past half-century. The main toxic components of DBL are furanoditerpenoids diosbulbin B (DSB) as well as 8-epidiosbulbin E (EEA). This toxic effect requires metabolic oxidation of the furan ring mediated by cytochrome P450 enzymes, and the P450 3A subfamily is the main enzyme responsible for the reported hepatotoxicity. <i>cis</i>-Enedial intermediates resulting from furan ring oxidation can react with nucleophilic sites of macromolecules, such as protein and DNA, which may trigger the toxicities. This review illustrates the liver injury induced by DBL including metabolic activation of DSB and EEA, the essential components responsible for DBL-induced hepatotoxicity, along with biochemical mechanisms of their toxic actions. It will facilitate the development of approaches to prevent and intervene in liver injury induced by DBL for its safe use in clinical practice.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"52 4","pages":"568-584"},"PeriodicalIF":5.9,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2020.1800724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38231544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiviral drugs and plasma therapy used for Covid-19 treatment: a nationwide Turkish algorithm.","authors":"Hayrunnisa Nadaroglu","doi":"10.1080/03602532.2020.1803907","DOIUrl":"https://doi.org/10.1080/03602532.2020.1803907","url":null,"abstract":"<p><p>The Coronavirus outbreak described as COVID-19 is an insidious and enormous biohazard which began to be noticed in November 2019. When the virus was determined to cause serious upper respiratory tract infections resulting in death, pandemics were declared in the world. As of today, the number of cases exceeded 221 thousand people in Turkey, the number of patients who died had reached 5526. In more than 200 countries around the world, 15.1 million people fight the disease, while the number of people recovered is over 9.134 million, and the number of deaths has exceeded 620 thousand. The top 5 countries in the world are USA, Brazil, Russia, India and Spain. The countries with the highest number of cases after America (approximately 4 million 28 thousand) are Brazil (approximately 2 million 166 thousand), India (about 1 million 195 thousand), Russia (approximately 789 thousand), South Africa (approximately 382 thousand). In addition, the number of deaths and cases caused by Covid 19 continues to increase day by day. In this review, it was aimed to discuss that Covidien-19 against antiviral drugs used in the struggle across the globe and plasma treatment options about the current state of knowledge and Turkey algorithm by comparing the therapeutic treatment options.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"52 4","pages":"531-539"},"PeriodicalIF":5.9,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/03602532.2020.1803907","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38233962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}