Compilation of 222 drugs’ plasma protein binding data and guidance for study designs

Zhang, Fengling; Xue, Jinpin; Shao, Jingwei; Li, Jia

doi:10.1016/j.drudis.2011.12.018

Cited by 181 publications

(167 citation statements)

References 51 publications

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“…Available techniques for measurement of protein binding include equilibrium dialysis, ultrafiltration, ultracentrifugation, microdialysis, chromatographic methods, capillary electrophoresis, fluorescence spectroscopy, and ultrafast immunoextraction. These methods have been compared extensively in published review articles, and only an overview is provided here (16,48,49). With the exception of microdialysis, which may be applied in vivo to measure unbound drug concentrations, these methods are used in vitro for protein binding determination.…”

Section: Protein Binding Determinationmentioning

confidence: 99%

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

2013

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SUMMARY For the optimization of dosing regimens of anti-infective agents, it is imperative to have a good understanding of pharmacokinetics (PK) and pharmacodynamics (PD). Whenever possible, drug efficacy needs to be related to unbound concentrations at the site of action. For anti-infective drugs, the infection site is typically located outside plasma, and a drug must diffuse through capillary membranes to reach its target. Disease- and drug-related factors can contribute to differential tissue distribution. As a result, the assumption that the plasma concentration of drugs represents a suitable surrogate of tissue concentrations may lead to erroneous conclusions. Quantifying drug exposure in tissues represents an opportunity to relate the pharmacologically active concentrations to an observed pharmacodynamic parameter, such as the MIC. Selection of an appropriate specimen to sample and the advantages and limitations of the available sampling techniques require careful consideration. Ultimately, the goal will be to assess the appropriateness of a drug and dosing regimen for a specific pathogen and infection.

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Section: Protein Binding Determinationmentioning

confidence: 99%

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

2013

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“…C free is calculated in the same way as described previously, using fiber constant. Experimentally, it is recommended to perform plasma protein binding experiments at minimum of three concentrations with triplicate determinations at each concentration [1,21] although many studies in literature to date only report one concentration. The use of multiple concentrations helps to determine any changes in binding that depend on drug concentration, perhaps due to saturation of binding sites.…”

Section: Determination Of Plasma Protein Binding (% Ppb)mentioning

confidence: 99%

“…In blood, primary binding of drugs and metabolites occurs to highly abundant carrier proteins such as serum albumin (acidic, basic, and neutral drugs) and α-1-acidglycoprotein (basic drugs, and steroids) while some drugs can also bind globulins or lipoproteins (few lipophilic and basic drugs) [1,2]. The binding of a ligand to protein dictates its biological availability because ligand-protein complex cannot cross cell membranes or bind to receptors.…”

Section: Introductionmentioning

confidence: 99%

Solid-Phase Microextraction in Binding Studies

Vuckovic¹

2016

Solid Phase Microextraction

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This chapter briefly discusses how solid-phase microextraction (SPME) can be successfully implemented to accurately measure ligand-receptor binding constants, % plasma protein binding, blood-to-plasma distribution ratios, and free versus total analyte concentrations. The main practical considerations and assumptions to successfully apply SPME to binding studies are discussed in detail, including the effect of significant versus negligible depletion, extraction time, pH, and fiber fouling. The binding results obtained with SPME are compared to literature values and to other techniques used for binding determinations, and the advantages and disadvantages of different methods are clearly discussed. Recent applications of SPME in binding studies are highlighted, with the primary focus on binding studies in biological fluids and tissues since this application area is where SPME has been most extensively applied. Highlighted examples show that SPME has been successfully applied for ligands with both low and high binding affinities, for ligands with different affinities to multiple sites on a given receptor, to study differences in inter-species binding as well as partitioning coefficients for various tissue types. The importance of studying inter-individual variability of free concentrations in future studies is highlighted and can contribute to the development of personalized medicine.

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“…HSA (ca. 66 kDa and 585 aa (Fanali et al, 2012;Peters, 1996b)) represents approximately 60% of all plasma proteins, with a concentration ranging from 0.53 to 0.75 mM (Kratochwil et al, 2002;Zhang et al, 2012). HSA is known to bind preferentially to lipophilic, neutral, and/or acidic compounds (Liu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Modification of a PAMPA model to predict passive gastrointestinal absorption and plasma protein binding

Bujard

Voirol

Carrupt

et al. 2015

European Journal of Pharmaceutical Sciences

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Compilation of 222 drugs’ plasma protein binding data and guidance for study designs

Cited by 181 publications

References 51 publications

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

Solid-Phase Microextraction in Binding Studies

Modification of a PAMPA model to predict passive gastrointestinal absorption and plasma protein binding

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