Abstract
Drug transporters play an important role in the absorption, distribution, excretion and toxicity of both endogenous and exogenous compounds. Transporters may act as physiological ‘gatekeepers’ in the regulation of the pharmacological and/or toxicological effects of drugs by limiting distribution to tissues responsible for their effect and/or toxicity. This review will first provide a brief outline of the characteristics of membrane bound drug transporter families and their respective roles in regulating drug pharmacokinetics. This background then provides the context for a discussion of the characterization of a drug candidate as a substrate, inhibitor and/or inducer of drug transporter(s), followed by an assessment of the in vitro and in vivo preclinical methods used in drug discovery and development for screening molecules to identify potential transporter interactions. Finally, specific examples of the translation of in vitro findings to the in vivo effects are discussed to link the current understanding of the impact of drug transporters to clinical pharmacology. Thus, the goal is to provide the drug discovery scientist with a cadre of concepts, strategies, and tools for ultimately making rational decisions in drug design and delivery resulting in the optimization of drug concentrations at the target of pharmacology.
Keywords: Drug transporters, drug-drug interaction, high throughput screening, pharmacokinetics, absorption, assay development, preclinical models, drug disposition
Combinatorial Chemistry & High Throughput Screening
Title: Evaluation of Drug Transporter Interactions in Drug Discovery and Development
Volume: 13 Issue: 2
Author(s): Yurong Lai, Kathleen E. Sampson and Jeffrey C. Stevens
Affiliation:
Keywords: Drug transporters, drug-drug interaction, high throughput screening, pharmacokinetics, absorption, assay development, preclinical models, drug disposition
Abstract: Drug transporters play an important role in the absorption, distribution, excretion and toxicity of both endogenous and exogenous compounds. Transporters may act as physiological ‘gatekeepers’ in the regulation of the pharmacological and/or toxicological effects of drugs by limiting distribution to tissues responsible for their effect and/or toxicity. This review will first provide a brief outline of the characteristics of membrane bound drug transporter families and their respective roles in regulating drug pharmacokinetics. This background then provides the context for a discussion of the characterization of a drug candidate as a substrate, inhibitor and/or inducer of drug transporter(s), followed by an assessment of the in vitro and in vivo preclinical methods used in drug discovery and development for screening molecules to identify potential transporter interactions. Finally, specific examples of the translation of in vitro findings to the in vivo effects are discussed to link the current understanding of the impact of drug transporters to clinical pharmacology. Thus, the goal is to provide the drug discovery scientist with a cadre of concepts, strategies, and tools for ultimately making rational decisions in drug design and delivery resulting in the optimization of drug concentrations at the target of pharmacology.
Export Options
About this article
Cite this article as:
Lai Yurong, Sampson E. Kathleen and Stevens C. Jeffrey, Evaluation of Drug Transporter Interactions in Drug Discovery and Development, Combinatorial Chemistry & High Throughput Screening 2010; 13 (2) . https://dx.doi.org/10.2174/138620710790596772
DOI https://dx.doi.org/10.2174/138620710790596772 |
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
-
Malignant Mesothelioma: Cell Survival Pathways and Radiation Therapy
Current Respiratory Medicine Reviews Recent Advances in the Synthesis and Development of Curcumin, its Combinations and Formulations and Curcumin-like Compounds as Anti-infective Agents
Current Medicinal Chemistry Targeting Protein Kinase Inhibitors with Traditional Chinese Medicine
Current Drug Targets Interactions of Cisplatin with non-DNA Targets and their Influence on Anticancer Activity and Drug Toxicity: The Complex World of the Platinum Complex
Current Cancer Drug Targets Inhibition of Disulfide Reductases as a Therapeutic Strategy
Current Enzyme Inhibition Gene Expression Studies to Investigate Disease Mechanisms in Rheumatoid Arthritis: Does Angiogenesis Play a Role?
Current Rheumatology Reviews Dysfunction of Mitochondrial ATP Production As a Target for Personalized Cancer Therapy
Current Pharmacogenomics and Personalized Medicine The Renin Angiotensin System in the Regulation of Angiogenesis
Current Pharmaceutical Design Detection of Melatonin Production from the Intestinal Epithelium Using Electrochemical Methods
Current Pharmaceutical Design Simulated Microgravity Based Stem Cell Cultures Enhance Their Utility for Cell-Based Therapy
Current Biotechnology ABC Transporters: Unvalidated Therapeutic Targets in Cancer and the CNS
Anti-Cancer Agents in Medicinal Chemistry Biological and Chemical Diversity of Coral-Derived Microorganisms
Current Medicinal Chemistry Genetics and Ulcerative Colitis: What are the Clinical Implications?
Current Drug Targets MicroRNAs in Esophageal Adenocarcinoma: Functional Significance and Potential for the Development of New Molecular Disease Markers
Current Pharmaceutical Design Reversal of Cardiac Iron Loading and Dysfunction in Thalassemic Mice by Curcuminoids
Medicinal Chemistry IAPs as a Target for Anticancer Therapy
Current Cancer Drug Targets Meet the Editorial Board
Current Medicinal Chemistry Small Players With Big Roles: MicroRNAs as Targets to Inhibit Breast Cancer Progression
Current Drug Targets Crude Methanol Extract of Rosin Gum Exhibits Specific Cytotoxicity against Human Breast Cancer Cells via Apoptosis Induction
Anti-Cancer Agents in Medicinal Chemistry Viral Vectors for Gene-Directed Enzyme Prodrug Therapy
Current Gene Therapy