Abstract
This review describes methods for quantifying the binding of small molecule drug candidates to plasma proteins and the application of these methods in drug discovery and development. Particular attention is devoted to methods amenable to medium-to-high throughput analysis and those well suited for measurement of compounds that are highly protein bound. The methods reviewed herein include the conventional techniques of equilibrium dialysis, ultrafiltration and ultracentrifugation, as well as some more novel approaches utilizing micropartitioning and biosensorbased analysis. Additional concepts that are discussed include plasma protein structure, enantioselective protein binding, drug displacement, the effect of patient demographics and disease states on free (unbound) drug levels, and the influence of protein binding on drug candidate pharmacokinetics and pharmacodynamics. Practical considerations pertaining to the evaluation of highly protein bound drug candidates are also highlighted.
Keywords: Plasma protein binding, human serum albumin, pharmacokinetics, equilibrium dialysis, ultrafiltration, ultracentrifugation, optical biosensors and micropartitioning
Combinatorial Chemistry & High Throughput Screening
Title: Plasma Protein Binding in Drug Discovery and Development
Volume: 13 Issue: 2
Author(s): Monique L. Howard, John J. Hill, Gerald R. Galluppi and Matthew A. McLean
Affiliation:
Keywords: Plasma protein binding, human serum albumin, pharmacokinetics, equilibrium dialysis, ultrafiltration, ultracentrifugation, optical biosensors and micropartitioning
Abstract: This review describes methods for quantifying the binding of small molecule drug candidates to plasma proteins and the application of these methods in drug discovery and development. Particular attention is devoted to methods amenable to medium-to-high throughput analysis and those well suited for measurement of compounds that are highly protein bound. The methods reviewed herein include the conventional techniques of equilibrium dialysis, ultrafiltration and ultracentrifugation, as well as some more novel approaches utilizing micropartitioning and biosensorbased analysis. Additional concepts that are discussed include plasma protein structure, enantioselective protein binding, drug displacement, the effect of patient demographics and disease states on free (unbound) drug levels, and the influence of protein binding on drug candidate pharmacokinetics and pharmacodynamics. Practical considerations pertaining to the evaluation of highly protein bound drug candidates are also highlighted.
Export Options
About this article
Cite this article as:
Howard L. Monique, Hill J. John, Galluppi R. Gerald and McLean A. Matthew, Plasma Protein Binding in Drug Discovery and Development, Combinatorial Chemistry & High Throughput Screening 2010; 13 (2) . https://dx.doi.org/10.2174/138620710790596745
DOI https://dx.doi.org/10.2174/138620710790596745 |
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
-
Involvement of Coagulation and Hemostasis in Inflammatory Bowel Diseases
Current Vascular Pharmacology Molecular Dissection of Renal Ischemia-Reperfusion: Oxidative Stress and Cellular Events
Current Medicinal Chemistry Periostin as a Heterofunctional Regulator of Cardiac Development and Disease
Current Genomics Effects of Lipid-Lowering Agents on Inflammation, Haemostasis and Blood Pressure
Current Pharmaceutical Design Chemotherapy and Cardiotoxicity in Hematologic Malignancies
Current Cancer Drug Targets Role of microRNAs in Vascular Remodeling
Current Molecular Medicine Group A Streptococcal Vaccine Candidates based on the Conserved Conformational Epitope from M Protein
Drug Delivery Letters Novel Therapeutic Approaches Targeting Matrix Metalloproteinases in Cardiovascular Disease
Current Topics in Medicinal Chemistry Relaxin as a Cardiovascular Hormone: Physiology, Pathophysiology and Therapeutic Promises
Cardiovascular & Hematological Agents in Medicinal Chemistry Current Options for the Pharmacotherapy of Obesity
Current Pharmaceutical Design G Protein-Coupled Receptors in Regulation of Body Weight
CNS & Neurological Disorders - Drug Targets The Role of the Osteoprotegerin/RANKL/RANK System in Diabetic Vascular Disease
Current Medicinal Chemistry Headspace Analyses in Valuable and Functional Foods: Application of SPME in the Quality Control and Characterization of Olive Oils
Current Analytical Chemistry Cellular Protection and Therapeutic Potential of Tocotrienols
Current Pharmaceutical Design Anti-Inflammatory and Antioxidant Properties of Piper Species: A Perspective from Screening to Molecular Mechanisms
Current Topics in Medicinal Chemistry Planar Cell Polarity Signaling in Collective Cell Movements During Morphogenesis and Disease
Current Genomics Diabetic Peripheral Neuropathy: Diagnosis and Treatment
Current Drug Safety Decrease in Secondary Neck Vessels in Multiple Sclerosis: A 5-year Longitudinal Magnetic Resonance Angiography Study
Current Neurovascular Research The Crosstalk Between miRNA and Mammalian Circadian Clock
Current Medicinal Chemistry Inflammation, High Density Lipoprotein and Endothelium
Current Medicinal Chemistry