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Investigating the Association between CYP2J2 Inhibitors and QT Prolongation: A Literature Review Drug Metab. Rev. (IF 5.9) Pub Date : 2024-03-13 Alexandra M. Wiley, Jade Yang, Rivcka Madhani, Abhinav Nath, Rheem A. Totah
Drug withdrawal post-marketing due tocardiotoxicity is a major concern for drug developers, regulatory agencies, and patients. One common mechanism of cardiotoxicity isthroughinhibition of cardiac ...
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Favipiravir, remdesivir, and lopinavir: metabolites, degradation products and their analytical methods Drug Metab. Rev. (IF 5.9) Pub Date : 2024-03-06 Mir Saleh Hoseininezhad-Namin, Elaheh Rahimpour, Abolghasem Jouyban
Severe acute respiratory syndrome 2 (SARS-CoV-2) caused the emergence of the COVID-19 pandemic all over the world. Several studies have suggested that antiviral drugs such as favipiravir (FAV), rem...
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Metabolic bioactivation of antidepressants: advance and underlying hepatotoxicity Drug Metab. Rev. (IF 5.9) Pub Date : 2024-02-04 Saleh M. Khalil, Kevin R. MacKenzie, Mirjana Maletic-Savatic, Feng Li
Many drugs that serve as first-line medications for the treatment of depression are associated with severe side effects, including liver injury. Of the 34 antidepressants discussed in this review, ...
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Melatonin in cancer biology: pathways, derivatives, and the promise of targeted delivery Drug Metab. Rev. (IF 5.9) Pub Date : 2024-01-30 Yu-juan Yi, Hong Tang, Peng-lai Pi, Han-wen Zhang, Si-yu Du, Wei-ye Ge, Qi Dai, Zi-yan Zhao, Jia Li, Zheng Sun
Melatonin, historically recognized for its primary role in regulating circadian rhythms, has expanded its influence particularly due to its wide range of biological activities. It has firmly establ...
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The aminosalicylate - folate connection Drug Metab. Rev. (IF 5.9) Pub Date : 2024-01-17 Robert E. London
Two aminosalicylate isomers have been found to possess useful pharmacological behavior: p-aminosalicylate (PAS, 4AS) is an anti-tubercular agent that targets M. tuberculosis, and 5-aminosalicylate ...
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The potential impact of CYP and UGT drug-metabolizing enzymes on brain target site drug exposure Drug Metab. Rev. (IF 5.9) Pub Date : 2024-01-10 Mengxu Zhang, Vivi Rottschäfer, Elizabeth C. M. de Lange
Drug metabolism is one of the critical determinants of drug disposition throughout the body. While traditionally associated with the liver, recent research has unveiled the presence and functional ...
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Enantioselectivity in some physiological and pathophysiological roles of hydroxyeicosatetraenoic acids Drug Metab. Rev. (IF 5.9) Pub Date : 2023-11-21 Sara A. Helal, Samar H. Gerges, Ayman O. S. El-Kadi
The phenomenon of chirality has been shown to greatly impact drug activities and effects. Different enantiomers may exhibit different effects in a certain biological condition or disease state. Cyt...
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Biopolymers as promising vehicles for drug delivery to the brain Drug Metab. Rev. (IF 5.9) Pub Date : 2023-11-14 Rajeswara Babu Mythri, Mysore Rajeswara Babu Aishwarya
The brain is a privileged organ, tightly guarded by a network of endothelial cells, pericytes, and glial cells called the blood brain barrier. This barrier facilitates tight regulation of the trans...
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Clinical pharmacokinetics of nebivolol: a systematic review Drug Metab. Rev. (IF 5.9) Pub Date : 2023-10-28 Nida Hanif, Ammara Zamir, Imran Imran, Hamid Saeed, Abdul Majeed, Anees ur Rehman, Waseem Ashraf, Faleh Alqahtani, Muhammad Fawad Rasool
Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmaco...
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Biotransformation research advances – 2022 year in review Drug Metab. Rev. (IF 5.9) Pub Date : 2023-10-28 S. Cyrus Khojasteh, Upendra A. Argikar, Lionel Cheruzel, Sungjoon Cho, Rachel D. Crouch, Deepika Dhaware, Carley J. S. Heck, Kevin M. Johnson, Amit S. Kalgutkar, Lloyd King, Joyce Liu, Bin Ma, Hlaing Maw, Grover P. Miller, Herana Kamal Seneviratne, Ryan H. Takahashi, Shuai Wang, Cong Wei, Klarissa D. Jackson
This annual review is the eighth of its kind since 2016 (Baillie et al. 2016, Khojasteh et al. 2017, Khojasteh et al. 2018, Khojasteh et al. 2019, Khojasteh et al. 2020, Khojasteh et al. 2021, Khoj...
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Pregnane X receptor as a therapeutic target for cholestatic liver injury Drug Metab. Rev. (IF 5.9) Pub Date : 2023-09-10 Huan Lan, Ying Zhang, Minqi Fan, Bingxin Wu, Caiyan Wang
Cholestatic liver injury (CLI) is caused by toxic bile acids (BAs) accumulation in the liver and can lead to inflammation and liver fibrosis. The mechanisms underlying CLI development remain unclea...
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Differential modulation of cytochrome P450 enzymes by arsenicals in non-human experimental models Drug Metab. Rev. (IF 5.9) Pub Date : 2023-09-07 Mahmoud A. El-Ghiaty, Sara R. El-Mahrouk, Mohammed A. Alqahtani, Ayman O. S. El-Kadi
Arsenic is a hazardous heavy metalloid that imposes threats to human health globally. It is widely spread throughout the environment in various forms. Arsenic-based compounds are either inorganic c...
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Drug transporters in drug disposition – the year 2022 in review Drug Metab. Rev. (IF 5.9) Pub Date : 2023-09-06 Paresh P. Chothe, Pallabi Mitra, Masanori Nakakariya, Diane Ramsden, Charles J. Rotter, Philip Sandoval, Kimio Tohyama
On behalf of all the authors, I am pleased to share our third annual review on drug transporter science with an emphasis on articles published and deemed influential in signifying drug transporters...
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New strategy for rational use of antihypertensive drugs in clinical practice in high-altitude hypoxic environments Drug Metab. Rev. (IF 5.9) Pub Date : 2023-08-24 Delong Duo, Yabin Duan, Junbo Zhu, Xue Bai, Jianxin Yang, Guiqin Liu, Qian Wang, Xiangyang Li
High-altitude hypoxic environments have critical implications on cardiovascular system function as well as blood pressure regulation. Such environments place patients with hypertension at risk by a...
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Bioactivation and reactivity research advances – 2022 year in review‡ Drug Metab. Rev. (IF 5.9) Pub Date : 2023-08-22 Shuai Wang, Upendra A. Argikar, Lionel Cheruzel, Sungjoon Cho, Rachel D. Crouch, Deepika Dhaware, Carley J. S. Heck, Kevin M. Johnson, Amit S. Kalgutkar, Lloyd King, Joyce Liu, Bin Ma, Hlaing Maw, Grover P. Miller, Herana Kamal Seneviratne, Ryan H. Takahashi, Cong Wei, S. Cyrus Khojasteh
With the 50th year mark since the launch of Drug Metabolism and Disposition journal, the field of drug metabolism and bioactivation has advanced exponentially in the past decades (Guengerich 2023)....
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Physiological and pathophysiological roles of hepoxilins and their analogs Drug Metab. Rev. (IF 5.9) Pub Date : 2023-06-01 Sara A. Helal, Fadumo Ahmed Isse, Samar H. Gerges, Ayman O. S. El-Kadi
Abstract The metabolism of arachidonic acid (AA) occurs via different pathways leading to the production of a great number of metabolites with a wide range of biological effects. Hepoxilins (HXs) are physiologically active AA metabolites produced through the lipoxygenase pathway. Since their discovery, several researchers have investigated their biological effects. They were proven to have pro-inflammatory
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Antitubercular drugs induced liver injury: an updated insight into molecular mechanisms Drug Metab. Rev. (IF 5.9) Pub Date : 2023-05-22 Devaraj Ezhilarasan
Abstract Tuberculosis (TB) remains a major global health burden. Antitubercular drugs (ATDs) such as isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol are used as first-line therapy in TB patients. Drug-induced liver injury is one of the common side effects that leads to the discontinuation of ATDs in TB patients. Therefore, this review discusses the molecular pathogenesis of ATDs
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The alteration of drug metabolism enzymes and pharmacokinetic parameters in nonalcoholic fatty liver disease: current animal models and clinical practice Drug Metab. Rev. (IF 5.9) Pub Date : 2023-04-28 Yan Zhu, Li Chen, Yuqi He, Lin Qin, Daopeng Tan, Zhaojun Bai, Yu Song, Yu-He Wang
Abstract Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. The whole concept of NAFLD has now moved into metabolic dysfunction-associated fatty liver disease (MAFLD) to emphasize the strong metabolic derangement as the basis of the disease. Several studies have suggested that hepatic gene expression was altered in NAFLD and NAFLD-related metabolic comorbidities, particularly
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Bufalin serves as a pharmaceutic that mitigates drug resistance Drug Metab. Rev. (IF 5.9) Pub Date : 2023-04-27 Linxuan Miao, Ying Liu, Nasra Mohamoud Ali, Yan Dong, Bin Zhang, Xiaonan Cui
Abstract Intrinsic or acquired drug resistance of tumor cells is the main cause of tumor chemotherapy failure and tumor-related death. Bufalin (BF) is the main active monomer component extracted from the Traditional Chinese Medicine Toad venom (secretions of glands behind the ears and epidermis of bufo gargarizans and Bufo Melanostictus Schneider). It is a cardiotonic steroid with broad-spectrum anti-cancer
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Plasma protein-mediated uptake and contradictions to the free drug hypothesis: a critical review Drug Metab. Rev. (IF 5.9) Pub Date : 2023-04-12 Julia Annette Schulz, David M. Stresser, John Cory Kalvass
Abstract According to the free drug hypothesis (FDH), only free, unbound drug is available to interact with biological targets. This hypothesis is the fundamental principle that continues to explain the vast majority of all pharmacokinetic and pharmacodynamic processes. Under the FDH, the free drug concentration at the target site is considered the driver of pharmacodynamic activity and pharmacokinetic
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Interaction of drugs with gut microbiota modulators Drug Metab. Rev. (IF 5.9) Pub Date : 2023-04-04 Dong-Hyun Kim
Abstract Orally administered drugs undergo four stages of absorption, distribution, metabolism, and excretion in the body. However, before being absorbed into the body, orally administered drugs contact with gut microbiota, which catalyze their metabolic reactions such as reduction, hydroxylation (including deconjugation), dehydrogenation, acetylation, etc. Although these metabolic reactions typically
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Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs Drug Metab. Rev. (IF 5.9) Pub Date : 2023-03-14 Amina Džidić-Krivić, Jasna Kusturica, Emina Karahmet Sher, Nejra Selak, Nejra Osmančević, Esma Karahmet Farhat, Farooq Sher
Abstract Gut microbiota is known as unique collection of microorganisms (including bacteria, archaea, eukaryotes and viruses) that exist in a complex environment of the gut. Recently, this has become one of the most popular areas of research in medicine because this plays not only an important role in disease development, but gut microbiota also influences drug pharmacokinetics. These alterations in
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Relationship between blood–brain barrier changes and drug metabolism under high-altitude hypoxia: obstacle or opportunity for drug transport? Drug Metab. Rev. (IF 5.9) Pub Date : 2023-02-23 Guiqin Liu, Xue Bai, Jianxin Yang, Yabin Duan, Junbo Zhu, Li Xiangyang
Abstract The blood–brain barrier is essential for maintaining the stability of the central nervous system and is also crucial for regulating drug metabolism, changes of blood–brain barrier’s structure and function can influence how drugs are delivered to the brain. In high-altitude hypoxia, the central nervous system’s function is drastically altered, which can cause disease and modify the metabolism
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Effects of xenobiotics on CYP1 enzyme-mediated biotransformation and bioactivation of estradiol Drug Metab. Rev. (IF 5.9) Pub Date : 2023-02-23 Xu Mao, Hui Li, Jiang Zheng
Abstract Endogenous estradiol (E2) exerts diverse physiological and pharmacological activities, commonly used for hormone replacement therapy. However, prolonged and excessive exposure to E2 potentially increases estrogenic cancer risk. Reportedly, CYP1 enzyme-mediated biotransformation of E2 is largely concerned with its balance between detoxification and carcinogenic pathways. Among the three key
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Molecular mechanisms of hepatotoxicity induced by compounds occurring in Evodiae Fructus Drug Metab. Rev. (IF 5.9) Pub Date : 2023-02-20 Caiqin Yan, Ting Peng, Tingting Zhang, Yuan Wang, Na Li, Kai Wang, Xijuan Jiang
Abstract Evodiae Fructus (EF) is a common herbal medicine with thousands of years of medicinal history in China, which has been demonstrated with many promising pharmacological effects on cancer, cardiovascular diseases and Alzheimer’s disease. However, there have been increasing reports of hepatotoxicity associated with EF consumption. Unfortunately, in a long term, many implicit constituents of EF
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3D self-assembled nanocarriers for drug delivery Drug Metab. Rev. (IF 5.9) Pub Date : 2023-02-10 Hossein Karballaei Mirzahosseini, Mojgan Sheikhi, Farhad Najmeddin, Mehrnoosh Shirangi, Mojtaba Mojtahedzadeh
Abstract There are many benefits to drug delivery from drug–carrier nanostructure systems. It might be developed to carefully control drug release rates or to deliver a precise amount of a therapeutic substance to particular body areas. Self-assembling is the process by which molecules and nanoparticles spontaneously organize into organized clusters. For instance, proteins and peptides can interact
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Effect of inflammation on cytochrome P450-mediated arachidonic acid metabolism and the consequences on cardiac hypertrophy Drug Metab. Rev. (IF 5.9) Pub Date : 2022-12-27 Mohammed A. W. ElKhatib, Fadumo Ahmed Isse, Ayman O. S. El-Kadi
Abstract The incidence of heart failure (HF) is generally preceded by cardiac hypertrophy (CH), which is the enlargement of cardiac myocytes in response to stress. During CH, the metabolism of arachidonic acid (AA), which is present in the cell membrane phospholipids, is modulated. Metabolism of AA gives rise to hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) via cytochrome
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Metabolic activation of tyrosine kinase inhibitors: recent advance and further clinical practice Drug Metab. Rev. (IF 5.9) Pub Date : 2022-12-01 Miao Yan, Wenqun Li, Wen-Bo Li, Qi Huang, Jing Li, Hua-Lin Cai, Hui Gong, Bi-Kui Zhang, Yi-Kun Wang
Abstract At present, receptor tyrosine kinase signaling-related pathways have been successfully mediated to inhibit tumor proliferation and promote anti-angiogenesis effects for cancer therapy. Tyrosine kinase inhibitors (TKIs), a group of novel chemotherapeutic agents, have been applied to treat diverse malignant tumors effectively. However, the latent toxic and side effects of TKIs, such as hepatotoxicity
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Aldehyde oxidase mediated drug metabolism: an underpredicted obstacle in drug discovery and development Drug Metab. Rev. (IF 5.9) Pub Date : 2022-11-12 Siva Nageswara Rao Gajula, Tanaaz Navin Nathani, Rashmi Madhukar Patil, Sasikala Talari, Rajesh Sonti
Abstract Aldehyde oxidase (AO) has garnered curiosity as a non-CYP metabolizing enzyme in drug development due to unexpected consequences such as toxic metabolite generation and high metabolic clearance resulting in the clinical failure of new drugs. Therefore, poor AO mediated clearance prediction in preclinical nonhuman species remains a significant obstacle in developing novel drugs. Various isoforms
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Cutting-edge strategies and critical advancements in characterization and quantification of metabolites concerning translational metabolomics Drug Metab. Rev. (IF 5.9) Pub Date : 2022-11-09 Megha Sajakumar Pillai, Sree Teja Paritala, Ravi P. Shah, Nitish Sharma, Pinaki Sengupta
Abstract Despite remarkable progress in drug discovery strategies, significant challenges are still remaining in translating new insights into clinical applications. Scientists are devising creative approaches to bridge the gap between scientific and translational research. Metabolomics is a unique field among other omics techniques for identifying novel metabolites and biomarkers. Fortunately, characterization
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Biotransformation novel advances – 2021 year in review Drug Metab. Rev. (IF 5.9) Pub Date : 2022-08-30 S. Cyrus Khojasteh, Upendra A. Argikar, Sungjoon Cho, Rachel Crouch, Carley J. S. Heck, Kevin M. Johnson, Amit S. Kalgutkar, Lloyd King, Hlaing (Holly) Maw, Herana Kamal Seneviratne, Shuai Wang, Cong Wei, Donglu Zhang, Klarissa D. Jackson
Abstract Biotransformation field is constantly evolving with new molecular structures and discoveries of metabolic pathways that impact efficacy and safety. Recent review by Kramlinger et al. (2022) nicely captures the future (and the past) of highly impactful science of biotransformation (see the first article). Based on the selected articles, this review was categorized into three sections: (1) new
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Targeting endothelial cell metabolism in cancerous microenvironment: a new approach for anti-angiogenic therapy Drug Metab. Rev. (IF 5.9) Pub Date : 2022-08-27 Parisa Mohammadi, Reza Yarani, Azam Rahimpour, Fatemeh Ranjbarnejad, Joana Mendes Lopes de Melo, Kamran Mansouri
Abstract Anti-angiogenic therapy is a practical approach to managing diseases with increased angiogenesis, such as cancer, maculopathies, and retinopathies. Considering the fundamental gaps in the knowledge of the vital pathways involved in angiogenesis and its inhibition and the insufficient efficiency of existing angiogenesis inhibitors, there is an increasing focus on the emergence of new therapeutic
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Epigenetics in drug disposition & drug therapy: symposium report of the 24th North American meeting of the International Society for the Study of Xenobiotics (ISSX) Drug Metab. Rev. (IF 5.9) Pub Date : 2022-08-24 Benjamin J. Maldonato, Ana G. Vergara, Jaydeep Yadav, Sarah M. Glass, Erickson M. Paragas, Dongying Li, Philip Lazarus, Joseph L. McClay, Baitang Ning, Ann K. Daly, Laura E. Russell
Abstract The 24th North American International Society for the Study of Xenobiotics (ISSX) meeting, held virtually from September 13 to 17, 2021, embraced the theme of “Broadening Our Horizons.” This reinforces a key mission of ISSX: striving to share innovative science related to drug discovery and development. Session speakers and the ISSX New Investigators Group, which supports the scientific and
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Bioactivation and reactivity research advances – 2021 year in review Drug Metab. Rev. (IF 5.9) Pub Date : 2022-08-05 Klarissa D. Jackson, Upendra A. Argikar, Sungjoon Cho, Rachel D. Crouch, James P. Driscoll, Carley J. S. Heck, Lloyd King, Hlaing (Holly) Maw, Grover P. Miller, Herana Kamal Seneviratne, Shuai Wang, Cong Wei, Donglu Zhang, S. Cyrus Khojasteh
Abstract This year’s review on bioactivation and reactivity began as a part of the annual review on biotransformation and bioactivation led by Cyrus Khojasteh (see references). Increased contributions from experts in the field led to the development of a stand alone edition for the first time this year focused specifically on bioactivation and reactivity. Our objective for this review is to highlight
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A transcriptional regulatory network of HNF4α and HNF1α involved in human diseases and drug metabolism Drug Metab. Rev. (IF 5.9) Pub Date : 2022-07-26 Jianxin Yang, Xue Bai, Guiqin Liu, Xiangyang Li
Abstract HNF4α and HNF1α are core transcription factors involved in the development and progression of a variety of human diseases and drug metabolism. They play critical roles in maintaining the normal growth and function of multiple organs, mainly the liver, and in the metabolism of endogenous and exogenous substances. The twelve isoforms of HNF4α may exhibit different physiological functions, and
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Novel insights in drug transporter sciences: the year 2021 in review Drug Metab. Rev. (IF 5.9) Pub Date : 2022-07-08 Paresh P. Chothe, Pallabi Mitra, Masanori Nakakariya, Diane Ramsden, Charles J. Rotter, Philip Sandoval, Kimio Tohyama
Abstract On behalf of the team I am pleased to present the second annual ‘novel insights into drug transporter sciences review’ focused on peer-reviewed articles that were published in the year 2021. In compiling the articles for inclusion, preprints available in 2021 but officially published in 2022 were considered to be in scope. To support this review the contributing authors independently selected
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Deoxynivalenol and its modified forms: key enzymes, inter-individual and interspecies differences in metabolism Drug Metab. Rev. (IF 5.9) Pub Date : 2022-06-21 Yating Wang, Jiefeng Li, Xu Wang, Wenda Wu, Eugenie Nepovimova, Qinghua Wu, Kamil Kuca
Abstract Deoxynivalenol (DON) and its modified forms, including DON-3-glucoside (DON-3G), pose a major agricultural and food safety issue in the world. Their metabolites are relatively well-characterized; however, their metabolizing enzymes have not been fully explored. UDP-glucuronosyltransferases, 3-O-acetyltransferase, and glutathione S-transferase are involved in the formation of DON-glucuronides
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The role of UDP-glycosyltransferases in xenobioticresistance Drug Metab. Rev. (IF 5.9) Pub Date : 2022-06-12 Diana Dimunová, Petra Matoušková, Radka Podlipná, Iva Boušová, Lenka Skálová
Abstract Uridine diphosphate sugar-utilizing glycosyltransferases (UGTs) are an enzyme superfamily that catalyzes glycosyl residues transfer from activated nucleotide sugars to acceptor molecules. In addition to various endogenous compounds, numerous xenobiotics are substrates of UGTs. As the glycosides formed are generally less active/toxic and more hydrophilic than aglycones, UGTs effectively protect
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Metabolism of the areca alkaloids – toxic and psychoactive constituents of the areca (betel) nut Drug Metab. Rev. (IF 5.9) Pub Date : 2022-05-29 Alan L. Myers
Abstract Areca nut (AN) is consumed by millions of people for its therapeutic and psychoactive effects, making it one of the most widely self-administered psychoactive substances in the world. Even so, AN use/abuse is associated with myriad oral and systemic side effects, affecting most organ systems in the body. Alkaloids abundant in the nut (e.g. arecoline, arecaidine, guvacoline, and guvacine),
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Impact of DNA methylation on ADME gene expression, drug disposition, and efficacy Drug Metab. Rev. (IF 5.9) Pub Date : 2022-05-08 Xu Hao, Yuanyuan Li, Jialu Bian, Ying Zhang, Shiyu He, Feng Yu, Yufei Feng, Lin Huang
Abstract Interindividual differences in drug response have always existed in clinical treatment. Genes involved in drug absorption, distribution, metabolism, and excretion (ADME) play an important role in the process of pharmacokinetics. The effects of genetic polymorphism and nuclear receptors on the expression of drug metabolism enzymes and transporters can only explain some individual differences
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In vitro cell-based models of drug-induced hepatotoxicity screening: progress and limitation Drug Metab. Rev. (IF 5.9) Pub Date : 2022-04-22 Maryam Mirahmad, Reyhaneh Sabourian, Mohammad Mahdavi, Bagher Larijani, Maliheh Safavi
Abstract Drug-induced liver injury (DILI) is one of the major causes of post-approval withdrawal of therapeutics. As a result, there is an increasing need for accurate predictive in vitro assays that reliably detect hepatotoxic drug candidates while reducing drug discovery time, costs, and the number of animal experiments. In vitro hepatocyte-based research has led to an improved comprehension of the
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Cell-Biomaterial constructs for wound healing and skin regeneration Drug Metab. Rev. (IF 5.9) Pub Date : 2022-04-02 Ingrid Safina, Luke T. Childress, Srinivas R. Myneni, Kieng Bao Vang, Alexandru S. Biris
Abstract Over the years, conventional skin grafts, such as full-thickness, split-thickness, and pre-sterilized grafts from human or animal sources, have been at the forefront of skin wound care. However, these conventional grafts are associated with major challenges, including supply shortage, rejection by the immune system, and disease transmission following transplantation. Due to recent progress
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The multifaceted role of cytochrome P450-Derived arachidonic acid metabolites in diabetes and diabetic cardiomyopathy Drug Metab. Rev. (IF 5.9) Pub Date : 2022-03-21 Fadumo Ahmed Isse, Ahmed A. El-Sherbeni, Ayman O. S. El-Kadi
Abstract Understanding lipid metabolism is a critical key to understanding the pathogenesis of Diabetes Mellitus (DM). It is known that 60–90% of DM patients are obese or used to be obese. The incidence of obesity is rising owing to the modern sedentary lifestyle that leads to insulin resistance and increased levels of free fatty acids, predisposing tissues to utilize more lipids with less glucose
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Regulation of human UDP-glycosyltransferase (UGT) genes by miRNAs Drug Metab. Rev. (IF 5.9) Pub Date : 2022-03-11 Dong Gui Hu, Peter I. Mackenzie, Julie-Ann Hulin, Ross A. McKinnon, Robyn Meech
Abstract The human UGT gene superfamily is divided into four subfamilies (UGT1, UGT2, UGT3 and UGT8) that encodes 22 functional enzymes. UGTs are critical for the metabolism and clearance of numerous endogenous and exogenous compounds, including steroid hormones, bile acids, bilirubin, fatty acids, carcinogens, and therapeutic drugs. Therefore, the expression and activities of UGTs are tightly regulated
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Implication of metabolomics and transporter modulation based strategies to minimize multidrug resistance and enhance site-specific bioavailability: a needful consideration toward modern anticancer drug discovery Drug Metab. Rev. (IF 5.9) Pub Date : 2022-03-07 Megha Rachmale, Niraj Rajput, Tarang Jadav, Amit Kumar Sahu, Rakesh K. Tekade, Pinaki Sengupta
Abstract Induction of drug-metabolizing enzymes and efflux transporters (DMET) through activation of pregnane x receptor (PXR) is the primary factor involved in almost all bioavailability and drug resistance-related problems of anticancer drugs. PXR is a transcriptional regulator of many metabolizing enzymes and efflux transporters proteins like p-glycoprotein (p-gp), multidrug resistant protein 1
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Through a glass, darkly? HepaRG and HepG2 cells as models of human phase I drug metabolism Drug Metab. Rev. (IF 5.9) Pub Date : 2022-02-23 Lesley A. Stanley, C. Roland Wolf
Abstract The pharmacokinetic and safety assessment of drug candidates is becoming increasingly dependent upon in vitro models of hepatic metabolism and toxicity. Predominant among these is the HepG2 cell line, although HepaRG is becoming increasingly popular because of its perceived closer resemblance to human hepatocytes. We review the functionality of these cell lines in terms of Phase I protein
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GSTM1 and GSTT1 polymorphisms in healthy volunteers – a worldwide systematic review Drug Metab. Rev. (IF 5.9) Pub Date : 2022-02-15 Giovana Nakanishi, Laísa S. Bertagnolli, Murilo Pita-Oliveira, Mariana M. Scudeler, Sabrina Torres-Loureiro, Thaís Almeida-Dantas, Maria Laura C. Alves, Heithor S. Cirino, Fernanda Rodrigues-Soares
Abstract The GSTM1 and GSTT1 genes encode homonymous enzymes, which are responsible for the detoxification of several substances potentially harmful to the human body, such as air pollution, drugs, pesticides, and tobacco. However, some individuals may present a complete deletion of these genes and, consequently, an enzyme deficiency leading to an inadequate metabolism and, therefore, a higher susceptibility
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The annoying flaws of gerontological research Drug Metab. Rev. (IF 5.9) Pub Date : 2022-02-04 Magomed Khaidakov, Valeria Troshina, Dmitry Menglet, Yusef Yusef, Alexander Plotkin
Abstract Gerontological research has accelerated dramatically in the last few decades. However, despite increased public interest, federal funding, an army of researchers, and many notable discoveries and high-impact publications, the goal of achieving even a modest extension of human lifespan seems to be as far away as ever or, at best, remains within the realm of lifestyle and diet optimization efforts
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Mass spectrometry based protein biomarkers and drug target discovery and clinical diagnosis in Age-Related progressing neurodegenerative diseases Drug Metab. Rev. (IF 5.9) Pub Date : 2022-01-24 Ishita Agrawal, Pallavi Tripathi, Shyamasri Biswas
Abstract Neurodegenerative diseases correspond to overly complex health disorders that are driven by intersecting pathophysiology that are often trapped in vicious cycles of degeneration and cognitive decline. The usual diagnostic route of these diseases is based on postmortem examination that involves identifying pathology that is specific to the disease in the brain. However, in such cases, accurate
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The relationship between UGT1A1 gene & various diseases and prevention strategies Drug Metab. Rev. (IF 5.9) Pub Date : 2021-11-22 Dan Liu, Qi Yu, Qing Ning, Zhongqiu Liu, Jie Song
Abstract UDP-glucuronyltransferase 1A1 (UGT1A1) is a member of the Phase II metabolic enzyme family and the only enzyme that can metabolize detoxified bilirubin. Inactivation and very low activity of UGT1A1 in the liver can be fatal or lead to lifelong Gilbert’s syndrome (GS) and Crigler–Najjar syndrome (CN). To date, more than one hundred UGT1A1 polymorphisms have been discovered. Although most UGT1A1
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Extensive metabolism of flavonoids relevant to their potential efficacy on Alzheimer’s disease Drug Metab. Rev. (IF 5.9) Pub Date : 2021-10-01 Hongjun Xia
(2021). Extensive metabolism of flavonoids relevant to their potential efficacy on Alzheimer’s disease. Drug Metabolism Reviews: Vol. 53, No. 4, pp. 563-591.
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Recent advances in drug transporter sciences: highlights from the year 2020 Drug Metab. Rev. (IF 5.9) Pub Date : 2021-09-14 Paresh P. Chothe, Masanori Nakakariya, Charles J. Rotter, Philip Sandoval, Kimio Tohyama
Abstract Drug Metabolism Reviews has an impressive track record of providing scientific reviews in the area of xenobiotic biotransformation over 47 years. It has consistently proved to be resourceful to many scientists from pharmaceutical industry, academia, regulatory agencies working in diverse areas including enzymology, pharmacology, pharmacokinetics, and toxicology. Over the last 5 years Drug
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Rodent genetic models of Ah receptor signaling Drug Metab. Rev. (IF 5.9) Pub Date : 2021-08-25 Rachel H. Wilson, Christopher A. Bradfield
Abstract The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that is a member of the PER-ARNT-SIM superfamily of environmental sensors. This receptor has been a molecule of interest for many years in the field of toxicology, as it was originally discovered to mediate the toxic effects of certain environmental pollutants like benzo(a)pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin
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Bioanalytical strategies in drug discovery and development Drug Metab. Rev. (IF 5.9) Pub Date : 2021-08-23 Aarzoo Thakur, Zhiyuan Tan, Tsubasa Kameyama, Eman El-Khateeb, Shakti Nagpal, Stephanie Malone, Rohitash Jamwal, Chukwunonso K. Nwabufo
Abstract A reliable, rapid, and effective bioanalytical method is essential for the determination of the pharmacokinetic, pharmacodynamic, and toxicokinetic parameters that inform the safety and efficacy profile of investigational drugs. The overall goal of bioanalytical method development is to elucidate the procedure and operating conditions under which a method can sufficiently extract, qualify
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Drug metabolic stability in early drug discovery to develop potential lead compounds Drug Metab. Rev. (IF 5.9) Pub Date : 2021-09-11 Siva Nageswara Rao Gajula, Nimisha Nadimpalli, Rajesh Sonti
Abstract Knowledge of the metabolic stability of a new drug substance eliminated by biotransformation is essential for envisaging the pharmacokinetic parameters required for deciding drug dosing and frequency. Strategies aimed at modifying lead compounds may improve metabolic stability, thereby reducing the drug dosing frequency. Replacement of selective hydrogens with deuterium can effectively enhance
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Introduction to the mini special issue on next generation drug discovery and development: rethinking translational pharmacology for accelerated drug development Drug Metab. Rev. (IF 5.9) Pub Date : 2021-05-07 Chukwunonso K. Nwabufo
Abstract The coronavirus disease (COVID-19) pandemic further revealed the barriers to accelerated discovery and development of transformative medicines for life threatening diseases. To effectively and efficiently respond to unmet medical needs, efforts should be directed towards revolutionizing the predictive capability of non-clinical surrogates that inform drug discovery and development programs
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Recent advances in computational metabolite structure predictions and altered metabolic pathways assessment to inform drug development processes Drug Metab. Rev. (IF 5.9) Pub Date : 2021-05-11 Mary Alexandra Schleiff, Deepika Dhaware, Jasleen K. Sodhi
Abstract Many drug candidates fail during preclinical and clinical trials due to variable or unexpected metabolism which may lead to variability in drug efficacy or adverse drug reactions. The drug metabolism field aims to address this important issue from many angles which range from the study of drug–drug interactions, pharmacogenomics, computational metabolic modeling, and others. This manuscript
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Recent developments in predicting CYP-independent metabolism Drug Metab. Rev. (IF 5.9) Pub Date : 2021-05-25 Nikhilesh V. Dhuria, Bianka Haro, Amit Kapadia, Khadjia A. Lobo, Bernice Matusow, Mary A. Schleiff, Christina Tantoy, Jasleen K. Sodhi
Abstract As lead optimization efforts have successfully reduced metabolic liabilities due to cytochrome P450 (CYP)-mediated metabolism, there has been an increase in the frequency of involvement of non-CYP enzymes in the metabolism of investigational compounds. Although there have been numerous notable advancements in the characterization of non-CYP enzymes with respect to their localization, reaction
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Recent developments in in vitro and in vivo models for improved translation of preclinical pharmacokinetics and pharmacodynamics data Drug Metab. Rev. (IF 5.9) Pub Date : 2021-05-25 Jaydeep Yadav, Mehdi El Hassani, Jasleen Sodhi, Volker M. Lauschke, Jessica H. Hartman, Laura E. Russell
Abstract Improved pharmacokinetics/pharmacodynamics (PK/PD) prediction in the early stages of drug development is essential to inform lead optimization strategies and reduce attrition rates. Recently, there have been significant advancements in the development of new in vitro and in vivo strategies to better characterize pharmacokinetic properties and efficacy of drug leads. Herein, we review advances
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Prediction of drug-induced kidney injury in drug discovery Drug Metab. Rev. (IF 5.9) Pub Date : 2021-05-17 Priyanka Kulkarni
Abstract Drug induced kidney injury is one of the leading causes of failure of drug development programs in the clinic. Early prediction of renal toxicity potential of drugs is crucial to the success of drug candidates in the clinic. The dynamic nature of the functioning of the kidney and the presence of drug uptake proteins introduce additional challenges in the prediction of renal injury caused by