Influence of plasma protein binding kinetics on hepatic clearance assessed from a “tube” model and a “well-stirred” model

1981 ◽  
Vol 9 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Jens Aa. Jansen
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Hepatic Clearance ◽  
Binding Kinetics ◽  
Tube Model ◽  
Protein Binding Kinetics

Plasma protein binding kinetics of valproic acid over a broad dosage range: therapeutic implications

1993 ◽  
Vol 18 (3) ◽  
pp. 191-197 ◽  
Author(s):  
M. J. Gómez Bellver ◽  
M. J. Garcéa Sánchez ◽  
A. C. Alonso Gonzalez ◽  
D. Santos Buelga ◽  
A. Dominguez–Gil
Keyword(s):  
Valproic Acid ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Binding Kinetics ◽  
Dosage Range ◽  
Therapeutic Implications ◽  
Protein Binding Kinetics ◽  
Kinetics Of

Plasma protein binding and endothelial enzyme interactions in the lung

1989 ◽  
Vol 66 (6) ◽  
pp. 2617-2628 ◽  
Author(s):  
J. H. Linehan ◽  
C. A. Dawson ◽  
R. D. Bongard ◽  
T. A. Bronikowski ◽  
D. L. Roerig
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Dissociation Rate ◽  
Binding Kinetics ◽  
Dilution Method ◽  
Bolus Transit ◽  
Protein Binding Kinetics ◽  
Transient Plasma ◽  
Kinetics Of

The influence of plasma albumin binding of the synthetic angiotensin-converting enzyme (ACE) substrate [3H]benzoyl-phenylalanyl-alanyl-proline (BPAP) on BPAP hydrolysis by pulmonary endothelial ACE was studied in isolated rabbit lungs perfused with a salt solution containing either 5% bovine serum albumin (BSA) or 5% dextran. The single-pass indicator-dilution method was used to measure the fraction (M) of [3H]BPAP hydrolyzed. Lung M was greater with albumin-free perfusate than when BSA was present. M decreased as the time (ti) that the BPAP was in contact with the BSA before reaching the lung was increased, suggesting that some BSA binding sites for BPAP were not in equilibrium during bolus transit through the lungs. The M vs. ti data were correlated using a model incorporating both rapid and slow binding kinetics of BPAP and BSA. For the slow BPAP-BSA interaction, the dissociation rate constant was approximately 0.015 s-1, and the fraction of the BPAP bound to these slowly equilibrating sites at equilibrium was approximately 22%. The results indicate that transient plasma protein binding kinetics can affect lung BPAP hydrolysis.

Possible therapeutic interventions in COVID-19 induced ARDS by cotinine as an ACE-2 promoter and AT-1R blocker

2020 ◽  
Vol 20 ◽  
Author(s):  
Tarun Sharma ◽  
Sidharth Mehan
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Distress Syndrome ◽  
Therapeutic Interventions ◽  
Promising Candidate ◽  
Angiotensin Converting Enzyme 2 ◽  
Proinflammatory Effect ◽  
Pulmonary Permeability

: In these challenging times of the pandemic, as coronavirus disease 2019 (COVID-19) has taken over the planet, its complications such as acute respiratory distress syndrome (ARDS) have the potential to wipe out a large portion of our population. Whereas a serious lack of ventilators, vaccine being months away makes the condition even worse. That's why promising drug therapy is required. One of them was suggested in this article. It is the angiotensin-converting enzyme-2 (ACE-2) to which the COVID-19 virus binds and upon downregulation of which the pulmonary permeability increases and results in the filling of alveoli by proteinaceous fluids, which finally results in ARDS. ARDS can be assisted by angiotensinII type-1 receptor (AT-1R) blocker and ACE-2 upregulator. AT-1R blocker will prevent vasoconstriction, the proinflammatory effect seen otherwise upon its activation. ACE-2 upregulation will ensure less formation of angiotensin II, vasodilatory effects due to the formation of angiotensin (1-7), increased breakdown of bradykinin at lung level. Overall, decreased vasoconstriction of vessels supplying lungs and decreased vasodilation of lung tissues will ensure decreased pulmonary permeability and eventually relieve ARDS. It should also be considered that all components of the reninangiotensin-aldosterone system (RAAS) are located in the lung tissues. A drug with the least plasma protein binding is required to ensure its distribution across these lung tissues. Cotinine appears to be a promising candidate for COVID-19- induced ARDS. It acts across the board and acts as both an AT-1R blocker, ACE-2 upregulator. It also has a weak plasma protein binding that helps to spread through the lung tissues. In this review, we summarized that cotinine, along with COVID-19 virus replication blocker anti-virals, may prove to be a promising therapy for the treatment of COVID-19 induced ARDS.

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