Drug Metabolism Reviews最新文献_第7页

Relationship between blood-brain barrier changes and drug metabolism under high-altitude hypoxia: obstacle or opportunity for drug transport? 高原缺氧条件下血脑屏障变化与药物代谢的关系:药物转运的障碍还是机遇?

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 DOI: 10.1080/03602532.2023.2180028

Guiqin Liu, Xue Bai, Jianxin Yang, Yabin Duan, Junbo Zhu, Li Xiangyang

{"title":"Relationship between blood-brain barrier changes and drug metabolism under high-altitude hypoxia: obstacle or opportunity for drug transport?","authors":"Guiqin Liu, Xue Bai, Jianxin Yang, Yabin Duan, Junbo Zhu, Li Xiangyang","doi":"10.1080/03602532.2023.2180028","DOIUrl":"https://doi.org/10.1080/03602532.2023.2180028","url":null,"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 of drugs in vivo. Changes in the structure and function of the blood-brain barrier and the transport of the drug across the blood-brain barrier under high-altitude hypoxia, are regulated by changes in brain microvascular endothelial cells, astrocytes, and pericytes, either regulated by drug metabolism factors such as drug transporters and drug-metabolizing enzymes. This article aims to review the effects of high-altitude hypoxia on the structure and function of the blood-brain barrier as well as the effects of changes in the blood-brain barrier on drug metabolism. We also hypothesized and explore the regulation and potential mechanisms of the blood-brain barrier and associated pathways, such as transcription factors, inflammatory factors, and nuclear receptors, in regulating drug transport under high-altitude hypoxia.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"107-125"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9501098","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}

引用次数: 1

Metabolic activation of tyrosine kinase inhibitors: recent advance and further clinical practice. 酪氨酸激酶抑制剂的代谢激活：最新进展和进一步临床实践。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 Epub Date: 2022-12-01 DOI: 10.1080/03602532.2022.2149775

Miao Yan, Wenqun Li, Wen-Bo Li, Qi Huang, Jing Li, Hua-Lin Cai, Hui Gong, Bi-Kui Zhang, Yi-Kun Wang

{"title":"Metabolic activation of tyrosine kinase inhibitors: recent advance and further clinical practice.","authors":"Miao Yan, Wenqun Li, Wen-Bo Li, Qi Huang, Jing Li, Hua-Lin Cai, Hui Gong, Bi-Kui Zhang, Yi-Kun Wang","doi":"10.1080/03602532.2022.2149775","DOIUrl":"10.1080/03602532.2022.2149775","url":null,"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 and cardiotoxicity, limit their use in clinical practice. Metabolic activation has the potential to lead to toxic effects. Numerous TKIs have been demonstrated to be transformed into chemically reactive/potentially toxic metabolites following cytochrome P450-catalyzed activation, which causes severe adverse reactions, including hepatotoxicity, cardiotoxicity, skin toxicity, immune injury, mitochondria injury, and cytochrome P450 inactivation. However, the precise mechanisms of how these chemically reactive/potentially toxic species induce toxicity remain poorly understood. In addition, we present our viewpoints that regulating the production of reactive metabolites may decrease the toxicity of TKIs. Exploring this topic will improve understanding of metabolic activation and its underlying mechanisms, promoting the rational use of TKIs. This review summarizes the updated evidence concerning the reactive metabolites of TKIs and the associated toxicities. This paper provides novel insight into the safe use of TKIs and the prevention and treatment of multiple TKIs adverse effects in clinical practice.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"94-106"},"PeriodicalIF":3.8,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183671","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}

引用次数: 0

3D self-assembled nanocarriers for drug delivery. 用于药物递送的三维自组装纳米载体。

IF 3.8 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 Epub Date: 2023-02-10 DOI: 10.1080/03602532.2023.2172182

Hossein Karballaei Mirzahosseini, Mojgan Sheikhi, Farhad Najmeddin, Mehrnoosh Shirangi, Mojtaba Mojtahedzadeh

{"title":"3D self-assembled nanocarriers for drug delivery.","authors":"Hossein Karballaei Mirzahosseini, Mojgan Sheikhi, Farhad Najmeddin, Mehrnoosh Shirangi, Mojtaba Mojtahedzadeh","doi":"10.1080/03602532.2023.2172182","DOIUrl":"10.1080/03602532.2023.2172182","url":null,"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 with one another to create highly organized supramolecular structures with various properties, such as helical ribbons and fibrous scaffolds. Another advantage of self-assembly is that it may be effective with a variety of materials, including metals, oxides, inorganic salts, polymers, semiconductors, and even organic semiconductors. Fullerene, graphene, and carbon nanotubes (CNTs), three of the most fundamental classes of three-dimensionally self-assembling nanostructured carbon-based materials, are essential for the development of modern nanotechnologies. Self-assembled nanomaterials are used in a variety of fields, including nanotechnology, imaging, and biosensors. This review study begins with a summary of various major 3D nanomaterials, including graphene oxide, CNTs, and nanodiamond, as well as 3D self-assembled polyfunctionalized nanostructures and adaptable nanocarriers for drug delivery.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"140-162"},"PeriodicalIF":3.8,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182021","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}

引用次数: 0

Effect of inflammation on cytochrome P450-mediated arachidonic acid metabolism and the consequences on cardiac hypertrophy. 炎症对细胞色素p450介导的花生四烯酸代谢的影响及其对心肌肥厚的影响。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 DOI: 10.1080/03602532.2022.2162075

Mohammed A W ElKhatib, Fadumo Ahmed Isse, Ayman O S El-Kadi

{"title":"Effect of inflammation on cytochrome P450-mediated arachidonic acid metabolism and the consequences on cardiac hypertrophy.","authors":"Mohammed A W ElKhatib, Fadumo Ahmed Isse, Ayman O S El-Kadi","doi":"10.1080/03602532.2022.2162075","DOIUrl":"https://doi.org/10.1080/03602532.2022.2162075","url":null,"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 P450 (CYP) ω-hydroxylases and CYP epoxygenases, respectively. A plethora of studies demonstrated the involvement of CYP-mediated AA metabolites in the pathogenesis of CH. Also, inflammation is known to be a characteristic hallmark of CH. In this review, our aim is to highlight the impact of inflammation on CYP-derived AA metabolites and CH. Inflammation is shown to modulate the expression of various CYP ω-hydroxylases and CYP epoxygenases and their respective metabolites in the heart. In general, HETEs such as 20-HETE and mid-chain HETEs are pro-inflammatory, while EETs are characterized by their anti-inflammatory and cardioprotective properties. Several mechanisms are implicated in inflammation-induced CH, including the modulation of NF-κB and MAPK. This review demonstrated the inflammatory modulation of cardiac CYPs and their metabolites in the context of CH and the anti-inflammatory strategies that can be employed in the treatment of CH and HF.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"50-74"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9553624","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}

引用次数: 4

Effects of xenobiotics on CYP1 enzyme-mediated biotransformation and bioactivation of estradiol. 外源药物对CYP1酶介导的雌二醇生物转化和生物活化的影响。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 DOI: 10.1080/03602532.2023.2177671

Xu Mao, Hui Li, Jiang Zheng

{"title":"Effects of xenobiotics on CYP1 enzyme-mediated biotransformation and bioactivation of estradiol.","authors":"Xu Mao, Hui Li, Jiang Zheng","doi":"10.1080/03602532.2023.2177671","DOIUrl":"https://doi.org/10.1080/03602532.2023.2177671","url":null,"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 CYP1 enzymes (CYP1A1, CYP1A2, and CYP1B1), CYP1A1 and CYP1A2 mainly catalyze the formation of nontoxic 2-hydroxyestradiol (2-OH-E2), while CYP1B1 specifically catalyzes the formation of genotoxic 4-hydroxyestradiol (4-OH-E2). 4-OH-E2 can be further metabolized to electrophilic quinone intermediates accompanied by the generation of reactive oxygen species (ROS), triggering DNA damage. Since abnormal alterations in CYP1 activities can greatly affect the bioactivation process of E2, regulatory effects of xenobiotics on CYP1s are essential for E2-associated cancer development. To date, thousands of natural and synthetic compounds have been found to show potential inhibition and/or induction actions on the three CYP1 members. Generally, these chemicals share similar planar polycyclic skeletons, the structural motifs and substituent groups of which are important for their inhibitory/inductive efficiency and selectivity toward CYP1 enzymes. This review comprehensively summarizes these known inhibitors and/or inductors of E2-metabolizing CYP1s based on chemical categories and discusses their structure-activity relationships, which would contribute to better understanding of the correlation between xenobiotic-regulated CYP1 activities and estrogenic cancer susceptibility.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"1-49"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9501095","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}

引用次数: 0

Molecular mechanisms of hepatotoxicity induced by compounds occurring in Evodiae Fructus. 枸杞子中化合物致肝毒性的分子机制。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2023-02-01 DOI: 10.1080/03602532.2023.2180027

Caiqin Yan, Ting Peng, Tingting Zhang, Yuan Wang, Na Li, Kai Wang, Xijuan Jiang

{"title":"Molecular mechanisms of hepatotoxicity induced by compounds occurring in Evodiae Fructus.","authors":"Caiqin Yan, Ting Peng, Tingting Zhang, Yuan Wang, Na Li, Kai Wang, Xijuan Jiang","doi":"10.1080/03602532.2023.2180027","DOIUrl":"https://doi.org/10.1080/03602532.2023.2180027","url":null,"abstract":"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 as well as their toxic mechanisms remain poorly understood. Recently, metabolic activation of hepatotoxic compounds of EF to generate reactive metabolites (RMs) has been implicated. Herein, we capture metabolic reactions relevant to hepatotoxicity of these compounds. Initially, catalyzed by the hepatic cytochrome P450 enzymes (CYP450s), the hepatotoxic compounds of EF are oxidized to generate RMs. Subsequently, the highly electrophilic RMs could react with nucleophilic groups contained in biomolecules, such as hepatic proteins, enzymes, and nucleic acids to form conjugates and/or adducts, leading to a sequence of toxicological consequences. In addition, currently proposed biological pathogenesis, including oxidative stress, mitochondrial damage and dysfunction, endoplasmic reticulum (ER) stress, hepatic metabolism disorder, and cell apoptosis are represented. In short, this review updates the knowledge on the pathways of metabolic activation of seven hepatotoxic compounds of EF and provides considerable insights into the relevance of proposed molecular hepatotoxicity mechanisms from a biochemical standpoint, for the purpose of providing a theoretical guideline for the rational application of EF in clinics.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"55 1-2","pages":"75-93"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9554140","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}

引用次数: 1

A transcriptional regulatory network of HNF4α and HNF1α involved in human diseases and drug metabolism. HNF4α和HNF1α参与人类疾病和药物代谢的转录调控网络。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2022-11-01 DOI: 10.1080/03602532.2022.2103146

Jianxin Yang, Xue Bai, Guiqin Liu, Xiangyang Li

引用次数: 0

Cutting-edge strategies and critical advancements in characterization and quantification of metabolites concerning translational metabolomics. 关于翻译代谢组学的代谢物表征和量化的前沿策略和关键进展。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2022-11-01 DOI: 10.1080/03602532.2022.2125987

Megha Sajakumar Pillai, Sree Teja Paritala, Ravi P Shah, Nitish Sharma, Pinaki Sengupta

{"title":"Cutting-edge strategies and critical advancements in characterization and quantification of metabolites concerning translational metabolomics.","authors":"Megha Sajakumar Pillai, Sree Teja Paritala, Ravi P Shah, Nitish Sharma, Pinaki Sengupta","doi":"10.1080/03602532.2022.2125987","DOIUrl":"https://doi.org/10.1080/03602532.2022.2125987","url":null,"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 and quantification of metabolites are becoming faster due to the progress in the field of orthogonal analytical techniques. This review detailed the advancement in the progress of sample preparation, and data processing techniques including data mining tools, database, and their quality control (QC). Advances in data processing tools make it easier to acquire unbiased data that includes a diverse set of metabolites. In addition, novel breakthroughs including, miniaturization as well as their integration with other devices, metabolite array technology, and crystalline sponge-based method have led to faster, more efficient, cost-effective, and holistic metabolomic analysis. The use of cutting-edge techniques to identify the human metabolite, including biomarkers has proven to be advantageous in terms of early disease identification, tracking the progression of illness, and possibility of personalized treatments. This review addressed the constraints of current metabolomics research, which are impeding the facilitation of translation of research from bench to bedside. Nevertheless, the possible way out from such constraints and future direction of translational metabolomics has been conferred.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"54 4","pages":"401-426"},"PeriodicalIF":5.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10364124","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}

引用次数: 0

Metabolism of the areca alkaloids - toxic and psychoactive constituents of the areca (betel) nut. 槟榔生物碱的代谢-槟榔(槟榔)果的毒性和精神活性成分。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2022-11-01 DOI: 10.1080/03602532.2022.2075010

Alan L Myers

{"title":"Metabolism of the areca alkaloids - toxic and psychoactive constituents of the areca (betel) nut.","authors":"Alan L Myers","doi":"10.1080/03602532.2022.2075010","DOIUrl":"https://doi.org/10.1080/03602532.2022.2075010","url":null,"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), collectively called the areca alkaloids, are presumably responsible for the major pharmacological effects experienced by users, with arecoline being the most abundant alkaloid with notable toxicological properties. However, the mechanisms of arecoline and other areca alkaloid elimination in humans remain poorly documented. Therefore, the purpose of this review is to provide an in-depth review of areca alkaloid pharmacokinetics (PK) in biological systems, and discuss mechanisms of metabolism by presenting information found in the literature. Also, the toxicological relevance of the known and purported metabolic steps will be reviewed. In brief, several areca alkaloids contain a labile methyl ester group and are susceptible to hydrolysis, although the human esterase responsible remains presumptive. Other notable mechanisms include N-oxidation, glutathionylation, nitrosamine conversion, and carbon-carbon double-bond reduction. These metabolic conversions result in toxic and sometimes less-toxic derivatives. Arecoline and arecaidine undergo extensive metabolism while far less is known about guvacine and guvacoline. Metabolism information may help predict drug interactions with human pharmaceuticals with overlapping elimination pathways. Altogether, this review provides a first-of-its-kind comprehensive analysis of AN alkaloid metabolism, adds perspective on new mechanisms of metabolism, and highlights the need for future metabolism work in the field.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"54 4","pages":"343-360"},"PeriodicalIF":5.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10362414","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}

引用次数: 5

Aldehyde oxidase mediated drug metabolism: an underpredicted obstacle in drug discovery and development. 醛氧化酶介导的药物代谢:药物发现和开发中一个被低估的障碍。

IF 5.9 2区医学

Drug Metabolism Reviews Pub Date : 2022-11-01 DOI: 10.1080/03602532.2022.2144879

Siva Nageswara Rao Gajula, Tanaaz Navin Nathani, Rashmi Madhukar Patil, Sasikala Talari, Rajesh Sonti

{"title":"Aldehyde oxidase mediated drug metabolism: an underpredicted obstacle in drug discovery and development.","authors":"Siva Nageswara Rao Gajula, Tanaaz Navin Nathani, Rashmi Madhukar Patil, Sasikala Talari, Rajesh Sonti","doi":"10.1080/03602532.2022.2144879","DOIUrl":"https://doi.org/10.1080/03602532.2022.2144879","url":null,"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 of AO, such as AOX1, AOX3, AOX3L1, and AOX4 exist across species, and different AO activity among humans influences the AO mediated drug metabolism. Therefore, carefully considering the unique challenges is essential in developing successful AO substrate drugs. The in vitro to in vivo extrapolation underpredicts AO mediated drug clearance due to the lack of reliable representative animal models, substrate-specific activity, and the discrepancy between absolute concentration and activity. An in vitro tool to extrapolate in vivo clearance using a yard-stick approach is provided to address the underprediction of AO mediated drug clearance. This approach uses a range of well-known AO drug substrates as calibrators for qualitative scaling new drugs into low, medium, or high clearance category drugs. So far, in vivo investigations on chimeric mice with humanized livers (humanized mice) have predicted AO mediated metabolism to the best extent. This review addresses the critical aspects of the drug discovery stage for AO metabolism studies, challenges faced in drug development, approaches to tackle AO mediated drug clearance's underprediction, and strategies to decrease the AO metabolism of drugs.","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":"54 4","pages":"427-448"},"PeriodicalIF":5.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10732703","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}

引用次数: 4