scholarly journals Bioanalysis for plasma protein binding studies in drug discovery and drug development: views and recommendations of the European Bioanalysis Forum

Bioanalysis ◽  
2014 ◽  
Vol 6 (5) ◽  
pp. 673-682 ◽  
Author(s):  
Brigitte Buscher ◽  
Sirpa Laakso ◽  
Hermann Mascher ◽  
Klaus Pusecker ◽  
Mira Doig ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Drug Development ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Binding Studies

scholarly journals Ultrafiltration Method for Plasma Protein Binding Studies and Its Limitations

Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 382
Author(s):  
Camelia-Maria Toma ◽  
Silvia Imre ◽  
Camil-Eugen Vari ◽  
Daniela-Lucia Muntean ◽  
Amelia Tero-Vescan
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Specific Binding ◽  
Critical Role ◽  
Volume Ratio ◽  
Binding Studies ◽  
Experimental Conditions ◽  
Key Aspects

Plasma protein binding plays a critical role in drug therapy, being a key part in the characterization of any compound. Among other methods, this process is largely studied by ultrafiltration based on its advantages. However, the method also has some limitations that could negatively influence the experimental results. The aim of this study was to underline key aspects regarding the limitations of the ultrafiltration method, and the potential ways to overcome them. The main limitations are given by the non-specific binding of the substances, the effect of the volume ratio obtained, and the need of a rigorous control of the experimental conditions, especially pH and temperature. This review presents a variety of methods that can hypothetically reduce the limitations, and concludes that ultrafiltration remains a reliable method for the study of protein binding. However, the methodology of the study should be carefully chosen.

The Role of Plasma Protein Binding in Drug Discovery

2007 ◽  
pp. 119-141 ◽  
Author(s):  
Roger E. Fessey ◽  
Rupert P. Austin ◽  
Patrick Barton ◽  
Andrew M. Davis ◽  
Mark C. Wenlock
Keyword(s):  
Drug Discovery ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein

scholarly journals Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 283
Author(s):  
Chengjun Jiang ◽  
Jie Li ◽  
Xianghai Cai ◽  
Nini Li ◽  
Yan Guo ◽  
...  
Keyword(s):  
Protein Binding ◽  
Tissue Distribution ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Equilibrium Dialysis ◽  
Free Fraction ◽  
Ultra Performance Liquid Chromatography ◽  
Sprague Dawley ◽  
Binding Studies ◽  
High Protein Binding

10-Dehydroxyl-12-demethoxy-conophylline is a natural anticancer candidate. The motivation of this study was to explore the pharmacokinetic profiles, tissue distribution, and plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline in Sprague Dawley rats. A rapid, sensitive, and specific ultra-performance liquid chromatography (UPLC) system with a fluorescence (FLR) detection method was developed for the determination of 10-dehydroxyl-12-demethoxy-conophylline in different rat biological samples. After intravenous (i.v.) dosing of 10-dehydroxyl-12-demethoxy-conophylline at different levels (4, 8, and 12 mg/kg), the half-life t1/2α of intravenous administration was about 7 min and the t1/2β was about 68 min. The AUC0→∞ increased in a dose-proportional manner from 68.478 μg/L·min for 4 mg/kg to 305.616 mg/L·min for 12 mg/kg. After intragastrical (i.g.) dosing of 20 mg/kg, plasma levels of 10-dehydroxyl-12-demethoxy-conophylline peaked at about 90 min. 10-dehydroxyl-12-demethoxy-conophyllinea absolute oral bioavailability was only 15.79%. The pharmacokinetics process of the drug was fit to a two-room model. Following a single i.v. dose (8 mg/kg), 10-dehydroxyl-12-demethoxy-conophylline was detected in all examined tissues with the highest in kidney, liver, and lung. Equilibrium dialysis was used to evaluate plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline at three concentrations (1.00, 2.50, and 5.00 µg/mL). Results indicated a very high protein binding degree (over 80%), reducing substantially the free fraction of the compound.

Species differences in drug plasma protein binding

MedChemComm ◽  
2014 ◽  
Vol 5 (7) ◽  
pp. 963-967 ◽  
Author(s):  
Nicola Colclough ◽  
Linette Ruston ◽  
J. Matthew Wood ◽  
Philip A. MacFaul
Keyword(s):  
Drug Discovery ◽  
Protein Binding ◽  
Human Plasma ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Plasma Proteins ◽  
Species Differences ◽  
Human Plasma Protein ◽  
Binding Data ◽  
Drug Plasma

Comparison of the human plasma protein binding data for a variety of drug discovery compounds indicates that compounds tend to be slightly more bound to human plasma proteins, than compared to plasma proteins from rats, dogs or mice.

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