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.
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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 |
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