Roflumilast analogs with improved metabolic stability, plasma protein binding, and pharmacokinetic profile

2019 ◽  
Vol 11 (6) ◽  
pp. 886-897 ◽  
Author(s):  
Bahia A. Moussa ◽  
Asmaa A. El‐Zaher ◽  
Mohamed K. El‐Ashrey ◽  
Marwa A. Fouad
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Pharmacokinetic Profile ◽  
Metabolic Stability

Cremophor EL Alters the Plasma Protein Binding and Pharmacokinetic Profile of Valspodar in Rats

Drug Research ◽  
2017 ◽  
Vol 67 (10) ◽  
pp. 591-595
Author(s):  
Ziyad Binkhathlan
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Pharmaceutical Formulations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Cremophor El ◽  
Unbound Fraction ◽  
Peg 400

AbstractCremophor EL is a nonionic surfactant widely used in pharmaceutical formulations. Nonetheless, there are several reports on the influence of this excipient on the protein binding, pharmacokinetics, and pharmacodynamics of drugs. Valspodar is an investigational non-immunosuppressive derivative of cyclosporine A, used in clinical trials for treatment of multidrug resistant tumors. The formulation of valspodar (Amdray®) contains cremophor EL and ethanol as solubilizing agents. The main aim of the current study was to assess the plasma protein binding (in vitro) and the pharmacokinetic profile of valspodar in the cremophor EL-based formulation in comparison to a cremophor EL-free formulation following intravenous (i. v.) administration to rats. Valspodar dissolved in PEG 400/ethanol (diluted in Dextrose 5%) was used as the cremophor EL-free formulation. The in vitro plasma unbound fraction (f u) of valspodar in the cremophor EL formulation was 2.3-fold higher than the PEG 400/ethanol formulation. Following a single i. v. dose of 5 mg/kg, valspodar in the cremophor EL-based formulation had around 50% lower plasma AUC compared to the PEG 400/ethanol formulation. Moreover, the cremophor EL formulation had significantly higher volume of distribution and clearance in comparison to the PEG 400-based formulation. The results highlight the significance of excipient-drug interaction that should not be overlooked during the early stages of drug development.

Bioavailability, plasma protein binding and metabolic stability studies of a ALDH2 activator, alda-1, using a validated LC-ESI-MS/MS method in rat plasma

RSC Advances ◽  
2015 ◽  
Vol 5 (67) ◽  
pp. 54395-54402 ◽  
Author(s):  
Isha Taneja ◽  
Kanumuri Siva Rama Raju ◽  
Monika Mittal ◽  
Kapil Dev ◽  
Mohammad Faheem Khan ◽  
...  
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Rat Plasma ◽  
Metabolic Stability ◽  
Stability Studies ◽  
Esi Ms

Alda-1 was found to be a poorly bioavailable, 82–86% protein bound, high extraction compound.

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.

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.

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