Toxicity mechanisms of nanoparticles in the male reproductive system
Drug Metab Rev. 2021 May 14:1-14. doi: 10.1080/03602532.2021.1917597. Online ahead of print.ABSTRACTThe field of nanotechnology has allowed for increasing nanoparticle (NP) exposure to the male reproductive system. Certain NPs have been reported to have adverse consequences on male germ and somatic cells. Germ cells are the bridge between generations and are responsible for the transmission of genetic and epigenetic information to future generations. A number of NPs have negative impacts on male germ and somatic cells which could ultimately affect fertility or the ability to produce healthy offspring. These impacts are rel...
Source: Drug Metabolism Reviews - May 14, 2021 Category: Drugs & Pharmacology Authors: Khaled Habas E şref Demir Chongye Guo Martin H Brinkworth Diana Anderson Source Type: research

Recent developments in < em > in vitro < /em > and < em > in vivo < /em > models for improved translation of preclinical pharmacokinetic and pharmacodynamics data
Drug Metab Rev. 2021 May 14:1-66. doi: 10.1080/03602532.2021.1922435. Online ahead of print.ABSTRACTImproved PK/PD prediction in 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 in experimental and mathematical models for clearance predictions, advancements in developing novel tools to capture slowly metabolized drugs, in vivo model developments to c...
Source: Drug Metabolism Reviews - May 14, 2021 Category: Drugs & Pharmacology Authors: Jaydeep Yadav Mehdi El Hassani Jasleen Sodhi Volker M Lauschke Jessica Hartman Laura Russell Source Type: research

Toxicity mechanisms of nanoparticles in the male reproductive system
Drug Metab Rev. 2021 May 14:1-14. doi: 10.1080/03602532.2021.1917597. Online ahead of print.ABSTRACTThe field of nanotechnology has allowed for increasing nanoparticle (NP) exposure to the male reproductive system. Certain NPs have been reported to have adverse consequences on male germ and somatic cells. Germ cells are the bridge between generations and are responsible for the transmission of genetic and epigenetic information to future generations. A number of NPs have negative impacts on male germ and somatic cells which could ultimately affect fertility or the ability to produce healthy offspring. These impacts are rel...
Source: Drug Metabolism Reviews - May 14, 2021 Category: Drugs & Pharmacology Authors: Khaled Habas E şref Demir Chongye Guo Martin H Brinkworth Diana Anderson Source Type: research

Recent developments in < em > in vitro < /em > and < em > in vivo < /em > models for improved translation of preclinical pharmacokinetic and pharmacodynamics data
Drug Metab Rev. 2021 May 14:1-66. doi: 10.1080/03602532.2021.1922435. Online ahead of print.ABSTRACTImproved PK/PD prediction in 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 in experimental and mathematical models for clearance predictions, advancements in developing novel tools to capture slowly metabolized drugs, in vivo model developments to c...
Source: Drug Metabolism Reviews - May 14, 2021 Category: Drugs & Pharmacology Authors: Jaydeep Yadav Mehdi El Hassani Jasleen Sodhi Volker M Lauschke Jessica Hartman Laura Russell Source Type: research

Toxicity mechanisms of nanoparticles in the male reproductive system
Drug Metab Rev. 2021 May 14:1-14. doi: 10.1080/03602532.2021.1917597. Online ahead of print.ABSTRACTThe field of nanotechnology has allowed for increasing nanoparticle (NP) exposure to the male reproductive system. Certain NPs have been reported to have adverse consequences on male germ and somatic cells. Germ cells are the bridge between generations and are responsible for the transmission of genetic and epigenetic information to future generations. A number of NPs have negative impacts on male germ and somatic cells which could ultimately affect fertility or the ability to produce healthy offspring. These impacts are rel...
Source: Drug Metabolism Reviews - May 14, 2021 Category: Drugs & Pharmacology Authors: Khaled Habas E şref Demir Chongye Guo Martin H Brinkworth Diana Anderson Source Type: research

Recent developments in < em > in vitro < /em > and < em > in vivo < /em > models for improved translation of preclinical pharmacokinetic and pharmacodynamics data
Drug Metab Rev. 2021 May 14:1-66. doi: 10.1080/03602532.2021.1922435. Online ahead of print.ABSTRACTImproved PK/PD prediction in 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 in experimental and mathematical models for clearance predictions, advancements in developing novel tools to capture slowly metabolized drugs, in vivo model developments to c...
Source: Drug Metabolism Reviews - May 14, 2021 Category: Drugs & Pharmacology Authors: Jaydeep Yadav Mehdi El Hassani Jasleen Sodhi Volker M Lauschke Jessica Hartman Laura Russell Source Type: research

Toxicity mechanisms of nanoparticles in the male reproductive system
Drug Metab Rev. 2021 May 14:1-14. doi: 10.1080/03602532.2021.1917597. Online ahead of print.ABSTRACTThe field of nanotechnology has allowed for increasing nanoparticle (NP) exposure to the male reproductive system. Certain NPs have been reported to have adverse consequences on male germ and somatic cells. Germ cells are the bridge between generations and are responsible for the transmission of genetic and epigenetic information to future generations. A number of NPs have negative impacts on male germ and somatic cells which could ultimately affect fertility or the ability to produce healthy offspring. These impacts are rel...
Source: Drug Metabolism Reviews - May 14, 2021 Category: Drugs & Pharmacology Authors: Khaled Habas E şref Demir Chongye Guo Martin H Brinkworth Diana Anderson Source Type: research

Recent developments in < em > in vitro < /em > and < em > in vivo < /em > models for improved translation of preclinical pharmacokinetic and pharmacodynamics data
Drug Metab Rev. 2021 May 14:1-66. doi: 10.1080/03602532.2021.1922435. Online ahead of print.ABSTRACTImproved PK/PD prediction in 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 in experimental and mathematical models for clearance predictions, advancements in developing novel tools to capture slowly metabolized drugs, in vivo model developments to c...
Source: Drug Metabolism Reviews - May 14, 2021 Category: Drugs & Pharmacology Authors: Jaydeep Yadav Mehdi El Hassani Jasleen Sodhi Volker M Lauschke Jessica Hartman Laura Russell Source Type: research

Transporter-mediated drug-drug interactions: Advancement in models, analytical tools and regulatory perspective
Drug Metab Rev. 2021 May 12:1-87. doi: 10.1080/03602532.2021.1928687. Online ahead of print.ABSTRACTDrug-drug interactions mediated by transporters are a serious clinical concern hence a tremendous amount of work has been done on the characterization of the transporter-mediated proteins in humans and animals. The underlying mechanism for the transporter-mediated drug-drug interaction is the induction or inhibition of transporter which is involved in the cellular uptake and efflux of drugs. Transporter of the brain, liver, kidney, and intestine are major determinants that alter the absorption, distribution, metabolism, excr...
Source: Drug Metabolism Reviews - May 13, 2021 Category: Drugs & Pharmacology Authors: Aishwarya Jala Srikanth Ponneganti Swetha Vishnubhatla Devi Gayathri Bhuvanam Prithvi Raju Mekala Bincy Varghese Radhakrishnanand Pullapanthula Ramu Adela Upadhyayula Suryanarayana Murty Roshan M Borkar Source Type: research

Reinforcing our defense or weakening the enemy? A comparative overview of defensive and offensive strategies developed to confront COVID-19
Drug Metab Rev. 2021 May 12:1-83. doi: 10.1080/03602532.2021.1928686. Online ahead of print.ABSTRACTDeveloping effective strategies to confront coronavirus disease 2019 (COVID-19) has become one of the greatest concerns of the scientific community. In addition to the vast number of global mortalities due to COVID-19, since its outbreak, almost every aspect of human lives has changed one way or another. In the present review, various defensive and offensive strategies developed to confront COVID-19 are illustrated. The Administration of immune-boosting micronutrients/agents, as well as the inhibition of the activity of inco...
Source: Drug Metabolism Reviews - May 13, 2021 Category: Drugs & Pharmacology Authors: Hamidreza Khodajou-Masouleh S Shirin Shahangian Behnam Rasti Source Type: research

Transporter-mediated drug-drug interactions: Advancement in models, analytical tools and regulatory perspective
Drug Metab Rev. 2021 May 12:1-87. doi: 10.1080/03602532.2021.1928687. Online ahead of print.ABSTRACTDrug-drug interactions mediated by transporters are a serious clinical concern hence a tremendous amount of work has been done on the characterization of the transporter-mediated proteins in humans and animals. The underlying mechanism for the transporter-mediated drug-drug interaction is the induction or inhibition of transporter which is involved in the cellular uptake and efflux of drugs. Transporter of the brain, liver, kidney, and intestine are major determinants that alter the absorption, distribution, metabolism, excr...
Source: Drug Metabolism Reviews - May 13, 2021 Category: Drugs & Pharmacology Authors: Aishwarya Jala Srikanth Ponneganti Swetha Vishnubhatla Devi Gayathri Bhuvanam Prithvi Raju Mekala Bincy Varghese Radhakrishnanand Pullapanthula Ramu Adela Upadhyayula Suryanarayana Murty Roshan M Borkar Source Type: research

Reinforcing our defense or weakening the enemy? A comparative overview of defensive and offensive strategies developed to confront COVID-19
Drug Metab Rev. 2021 May 12:1-83. doi: 10.1080/03602532.2021.1928686. Online ahead of print.ABSTRACTDeveloping effective strategies to confront coronavirus disease 2019 (COVID-19) has become one of the greatest concerns of the scientific community. In addition to the vast number of global mortalities due to COVID-19, since its outbreak, almost every aspect of human lives has changed one way or another. In the present review, various defensive and offensive strategies developed to confront COVID-19 are illustrated. The Administration of immune-boosting micronutrients/agents, as well as the inhibition of the activity of inco...
Source: Drug Metabolism Reviews - May 13, 2021 Category: Drugs & Pharmacology Authors: Hamidreza Khodajou-Masouleh S Shirin Shahangian Behnam Rasti Source Type: research

Introduction to the mini special issue on next generation drug discovery and development: rethinking translational pharmacology for accelerated drug development
Drug Metab Rev. 2021 May 7:1-2. doi: 10.1080/03602532.2021.1909614. Online ahead of print.ABSTRACTAbstratThe 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. I developed this mini special issue amidst the COVID-19 pandemic to evaluate recent advancements and opportunities for four main su...
Source: Drug Metabolism Reviews - May 8, 2021 Category: Drugs & Pharmacology Authors: Chukwunonso K Nwabufo Source Type: research

Recent developments in predicting CYP-Independent metabolism
Drug Metab Rev. 2021 May 4:1-69. doi: 10.1080/03602532.2021.1923728. Online ahead of print.ABSTRACTAs 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 mechanisms, species differences and identification of typical substrates, accurate prediction of non-CYP mediated clearance, with a pa...
Source: Drug Metabolism Reviews - May 4, 2021 Category: Drugs & Pharmacology Authors: Nikhilesh V Dhuria Bianka Haro Amit Kapadia Khadjia A Lobo Bernice Matusow Mary A Schleiff Christina Tantoy Jasleen K Sodhi Source Type: research

Novel Advances in Biotransformation and Bioactivation Research - 2020 year in review
Drug Metab Rev. 2021 Apr 28:1-91. doi: 10.1080/03602532.2021.1916028. Online ahead of print.ABSTRACTThis annual review is the sixth of its kind since 2016 (see references). Our objective is to explore and share articles which we deem influential and significant in the field of biotransformation and bioactivation. These fields are constantly evolving with new molecular structures and discoveries of corresponding pathways for metabolism that impact relevant drug development with respect to efficacy and safety. Based on the selected articles, we created three sections: (1) drug design, (2) metabolites and drug metabolizing en...
Source: Drug Metabolism Reviews - April 29, 2021 Category: Drugs & Pharmacology Authors: S Cyrus Khojasteh Upendra A Argikar James P Driscoll Carley J S Heck Lloyd King Klarissa D Jackson Wenying Jian Amit S Kalgutkar Grover P Miller Valerie Kramlinger Ivonne M C M Rietjens Aaron M Teitelbaum Kai Wang Cong Wei Source Type: research

Pharmacokinetics, toxicological and clinical aspects of ulipristal acetate: insights into the mechanisms implicated in the hepatic toxicity
Drug Metab Rev. 2021 Apr 27:1-9. doi: 10.1080/03602532.2021.1917599. Online ahead of print.ABSTRACTUlipristal acetate is a drug used as emergency contraceptive (30 mg) and for the treatment of moderate to severe symptoms of uterine myomas (5 mg). After commercialization, and although the exact number is unknown, serious cases implying ulipristal acetate 5 mg as a contributing factor of liver injury, some leading to transplantation, were reported. These cases prompted to a restrict use of the drug in January 2021 by the European Medicines Agency. This work aimed to fully review pharmacokinetic aspects, namely focusing in th...
Source: Drug Metabolism Reviews - April 27, 2021 Category: Drugs & Pharmacology Authors: Ricardo Jorge Dinis-Oliveira Source Type: research

Insights into oral bioavailability enhancement of therapeutic herbal constituents by cytochrome P450 3A inhibition
Drug Metab Rev. 2021 Apr 27:1-17. doi: 10.1080/03602532.2021.1917598. Online ahead of print.ABSTRACTHerbal plants typically have complex compositions and diverse mechanisms. Among them, bioactive constituents with relatively high exposure in vivo are likely to exhibit therapeutic efficacy. On the other hand, their bioavailability may be influenced by the synergistic effects of different bioactive components. Cytochrome P450 3A (CYP3A) is one of the most abundant CYP enzymes, responsible for the metabolism of 50% of approved drugs. In recent years, many therapeutic herbal constituents have been identified as CYP3A substrate...
Source: Drug Metabolism Reviews - April 27, 2021 Category: Drugs & Pharmacology Authors: Junmei Chen Jinman Liu Yueyue Huang Ruoyu Li Cuiru Ma Beiping Zhang Fanchang Wu Wenqian Yu Xue Zuo Yong Liang Qi Wang Source Type: research

Pharmacokinetics, toxicological and clinical aspects of ulipristal acetate: insights into the mechanisms implicated in the hepatic toxicity
Drug Metab Rev. 2021 Apr 27:1-9. doi: 10.1080/03602532.2021.1917599. Online ahead of print.ABSTRACTUlipristal acetate is a drug used as emergency contraceptive (30 mg) and for the treatment of moderate to severe symptoms of uterine myomas (5 mg). After commercialization, and although the exact number is unknown, serious cases implying ulipristal acetate 5 mg as a contributing factor of liver injury, some leading to transplantation, were reported. These cases prompted to a restrict use of the drug in January 2021 by the European Medicines Agency. This work aimed to fully review pharmacokinetic aspects, namely focusing in th...
Source: Drug Metabolism Reviews - April 27, 2021 Category: Drugs & Pharmacology Authors: Ricardo Jorge Dinis-Oliveira Source Type: research

Insights into oral bioavailability enhancement of therapeutic herbal constituents by cytochrome P450 3A inhibition
Drug Metab Rev. 2021 Apr 27:1-17. doi: 10.1080/03602532.2021.1917598. Online ahead of print.ABSTRACTHerbal plants typically have complex compositions and diverse mechanisms. Among them, bioactive constituents with relatively high exposure in vivo are likely to exhibit therapeutic efficacy. On the other hand, their bioavailability may be influenced by the synergistic effects of different bioactive components. Cytochrome P450 3A (CYP3A) is one of the most abundant CYP enzymes, responsible for the metabolism of 50% of approved drugs. In recent years, many therapeutic herbal constituents have been identified as CYP3A substrate...
Source: Drug Metabolism Reviews - April 27, 2021 Category: Drugs & Pharmacology Authors: Junmei Chen Jinman Liu Yueyue Huang Ruoyu Li Cuiru Ma Beiping Zhang Fanchang Wu Wenqian Yu Xue Zuo Yong Liang Qi Wang Source Type: research

Recent Advances in Computational Metabolite Structure Predictions and Altered Metabolic Pathways Assessment to Inform Drug Development Processes
Drug Metab Rev. 2021 Apr 12:1-37. doi: 10.1080/03602532.2021.1910292. Online ahead of print.ABSTRACTMany 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 aims to provide brief but comprehensive manuscript summaries highlighting the conclusions and scientific importance of seven exceptional...
Source: Drug Metabolism Reviews - April 12, 2021 Category: Drugs & Pharmacology Authors: Mary Alexandra Schleiff Deepika Dhaware Jasleen K Sodhi Source Type: research

International Society for the Study of Xenobiotics (ISSX) New Investigator Group Committee 2019-2020 concluding remarks
Drug Metab Rev. 2021 Apr 9:1-6. doi: 10.1080/03602532.2021.1910293. Online ahead of print.ABSTRACTThe International Society for the Study of Xenobiotics (ISSX) New Investigators Group has assembled a global team of emerging scientists to collaboratively compose a series of articles whose topics span the broad field of drug metabolism and will guide both new and established investigators alike. The New Investigator Group Committee members are proud to have provided such an opportunity to many promising early-career scientists from across the globe, and would like to acknowledge each contributor for their efforts.PMID:338361...
Source: Drug Metabolism Reviews - April 9, 2021 Category: Drugs & Pharmacology Authors: Mary A Schleiff Jasleen K Sodhi Source Type: research

Pharmacogenomics in the Era of Next Generation Sequencing - from Byte to Bedside
Drug Metab Rev. 2021 Apr 5:1-79. doi: 10.1080/03602532.2021.1909613. Online ahead of print.ABSTRACTPharmacogenetic research has resulted in the identification of a multitude of genetic variants that impact drug response or toxicity. These polymorphisms are mostly common and have been included as actionable information in the labels of numerous drugs. In addition to common variants, recent advances in Next Generation Sequencing (NGS) technologies have resulted in the identification of a plethora of rare and population-specific pharmacogenetic variations with unclear functional consequences that are not accessible by convent...
Source: Drug Metabolism Reviews - April 6, 2021 Category: Drugs & Pharmacology Authors: Laura E Russell Yitian Zhou Ahmed A Almousa Jasleen K Sodhi Chukwunonso K Nwabufo Volker M Lauschke Source Type: research

Ibuprofen-based advanced therapeutics: breaking the inflammatory link in cancer, neurodegeneration, and diseases
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 pathol...
Source: Drug Metabolism Reviews - April 6, 2021 Category: Drugs & Pharmacology Authors: Arun Upadhyay Ayeman Amanullah Vibhuti Joshi Rohan Dhiman Vijay Kumar Prajapati Krishna Mohan Poluri Amit Mishra Source Type: research

Pharmacogenomics in the Era of Next Generation Sequencing - from Byte to Bedside
Drug Metab Rev. 2021 Apr 5:1-79. doi: 10.1080/03602532.2021.1909613. Online ahead of print.ABSTRACTPharmacogenetic research has resulted in the identification of a multitude of genetic variants that impact drug response or toxicity. These polymorphisms are mostly common and have been included as actionable information in the labels of numerous drugs. In addition to common variants, recent advances in Next Generation Sequencing (NGS) technologies have resulted in the identification of a plethora of rare and population-specific pharmacogenetic variations with unclear functional consequences that are not accessible by convent...
Source: Drug Metabolism Reviews - April 6, 2021 Category: Drugs & Pharmacology Authors: Laura E Russell Yitian Zhou Ahmed A Almousa Jasleen K Sodhi Chukwunonso K Nwabufo Volker M Lauschke Source Type: research