Abstract
Drug metabolizing enzyme induction, or the process of generating excess drug metabolizing enzyme in important tissues of drug disposition such as liver and intestine, can give rise to pharmacokinetic situations whereby drug interactions occur. There are two major concerns associated with enzyme induction. First is the potential loss of efficacy due to more rapid metabolism and second is the risk of an increase in the formation of a potential reactive/toxic metabolite. Because of this, pharmaceutical companies consider enzyme induction as an undesired drug property for their potential drug candidates. As a consequence, the number of tools and models to evaluate induction of drug metabolizing enzymes has been increased tremendously over the past decade. As often is the case, every assay and approach has its own advantages and disadvantages and unfortunately, no single tool is currently available to predict the induction potential of drug candidates in humans. The purpose of this review is not only to outline the screening tools currently available for determining the induction potential of new chemical entities but also to translate these tools into a valuable screening strategy, covering aspects such as, induction liability assessment, structure-activity relationships (SAR), induction risk assessment and translating in vitro findings into clinical relevance.
Keywords: Induction, cytochrome P450, screening, assays, mechanism, drug-drug interactions
Combinatorial Chemistry & High Throughput Screening
Title: Enzyme Induction: Translating Multiple Approaches, Assays, Endpoints, and Opinions into a Valuable Induction Screening Strategy
Volume: 13 Issue: 2
Author(s): Adrian Fretland and Mario Monshouwer
Affiliation:
Keywords: Induction, cytochrome P450, screening, assays, mechanism, drug-drug interactions
Abstract: Drug metabolizing enzyme induction, or the process of generating excess drug metabolizing enzyme in important tissues of drug disposition such as liver and intestine, can give rise to pharmacokinetic situations whereby drug interactions occur. There are two major concerns associated with enzyme induction. First is the potential loss of efficacy due to more rapid metabolism and second is the risk of an increase in the formation of a potential reactive/toxic metabolite. Because of this, pharmaceutical companies consider enzyme induction as an undesired drug property for their potential drug candidates. As a consequence, the number of tools and models to evaluate induction of drug metabolizing enzymes has been increased tremendously over the past decade. As often is the case, every assay and approach has its own advantages and disadvantages and unfortunately, no single tool is currently available to predict the induction potential of drug candidates in humans. The purpose of this review is not only to outline the screening tools currently available for determining the induction potential of new chemical entities but also to translate these tools into a valuable screening strategy, covering aspects such as, induction liability assessment, structure-activity relationships (SAR), induction risk assessment and translating in vitro findings into clinical relevance.
Export Options
About this article
Cite this article as:
Fretland Adrian and Monshouwer Mario, Enzyme Induction: Translating Multiple Approaches, Assays, Endpoints, and Opinions into a Valuable Induction Screening Strategy, Combinatorial Chemistry & High Throughput Screening 2010; 13 (2) . https://dx.doi.org/10.2174/138620710790596727
DOI https://dx.doi.org/10.2174/138620710790596727 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
CD147/EMMPRIN and CD44 are Potential Therapeutic Targets for Metastatic Prostate Cancer
Current Cancer Drug Targets Tumour-Derived Glutamate: Linking Aberrant Cancer Cell Metabolism to Peripheral Sensory Pain Pathways
Current Neuropharmacology An Overview on the Different Approaches to Obtain Luminescent Hydrotalcite Nanoparticles and Films
Current Physical Chemistry Effects of Alcohol in the Lung
Current Respiratory Medicine Reviews Proteomic Validation of Protease Drug Targets: Pharmacoproteomics of Matrix Metalloproteinase Inhibitor Drugs Using Isotope-Coded Affinity Tag Labelling and Tandem Mass Spectrometry
Current Pharmaceutical Design Sirtuin Inhibitors: An Overview from Medicinal Chemistry Perspective
Anti-Cancer Agents in Medicinal Chemistry DNA Repair in Premature Aging Disorders and Neurodegeneration
Current Aging Science The role of Nox-mediated oxidation in the regulation of cytoskeletal dynamics
Current Pharmaceutical Design Targeting Cancer Stem Cells with Repurposed Drugs to Improve Current Therapies
Recent Patents on Anti-Cancer Drug Discovery Peptides Targeting Toll-Like Receptor Signalling Pathways for Novel Immune Therapeutics
Current Pharmaceutical Design Revisiting the ABCs of Multidrug Resistance in Cancer Chemotherapy
Current Pharmaceutical Biotechnology The Effects of 1,3,5-trisubstituted Indole Derivatives on Cell Growth, Apoptosis and MMP-2/9 mRNA Expression of MCF-7 Human Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Arginine Deprivation, Autophagy, Apoptosis (AAA) for the Treatment of Melanoma
Current Molecular Medicine Hypoxia Signaling and the Metastatic Phenotype
Current Molecular Medicine Rac-1 as a New Therapeutic Target in Cerebro- and Cardio-Vascular Diseases
Current Drug Targets Properties and Clinical Development of a Novel Coating Technology: The poly[bis(trifluoroethoxy)phosphazene]
Recent Patents on Drug Delivery & Formulation Profile of HBV Integration in the Plasma DNA of Hepatocellular Carcinoma Patients
Current Genomics Molecular Chaperone Activity and Biological Regulatory Actions of the TPR-Domain Immunophilins FKBP51 and FKBP52
Current Protein & Peptide Science Genetics and Bioenergetics of Mitochondria Influencing the Etiology and Pharmacology of Steroidal Hormones
Current Pharmacogenomics Androgen Receptor Cofactors in Prostate Cancer: Potential Therapeutic Targets of Castration-Resistant Prostate Cancer
Current Cancer Drug Targets