Influence of Maternal Plasma Protein Binding on Fetal Unbound Plasma Concentration of Propranolol in the Pregnant Ewe

1988 ◽  
Vol 77 (10) ◽  
pp. 835-837 ◽  
Author(s):  
Denis J. Morgan ◽  
George W. Mihaly ◽  
Mark A. Czuba ◽  
Michael S. Ching ◽  
Kenneth J. Hardy ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Maternal Plasma ◽  
Pregnant Ewe

Distribution, metabolism, excretion and toxicokinetics of vitexin in rats and dogs

2021 ◽  
Vol 17 ◽  
Author(s):  
Daopeng Tan ◽  
Geng Li ◽  
Wenying Lv ◽  
Xu Shao ◽  
Xiaoliang Li ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Intravenous Administration ◽  
Equilibrium Dialysis ◽  
Bioactive Compound ◽  
Repeated Administration ◽  
Time Curve ◽  
Suitable Alternative

Background: Vitexin is the main bioactive compound of hawthorn (Crataegus pinnatifida), a famous traditional Chinese medicine, and vitexin for injection is currently in phase I clinical trial in China. Objective: This investigation systematically evaluated the metabolism and toxicokinetics of vitexin in rats and dogs. Methods: Rats and beagle dogs were administrated different doses of vitexin, and then the plasma concentration, tissue distribution, excretion, metabolism, pharmacokinetics and plasma protein binding were investigated. Results : The elimination half-life (t1/2) values in rats after a single intravenous dose of 3, 15 and 75 mg/kg were estimated as 43.53±10.82, 22.86±4.23, and 21.17±8.64 min, and the values of the area under the plasma concentration-time curve (AUC0→∞) were 329.34±144.07, 974.79±177.27, and 5251.49±786.98 mg•min/L, respectively. The plasma protein binding rate in rats was determined as about 65% by equilibrium dialysis after 72 hr. After 24 hr of intravenous administration, 16.30%, 3.47% and 9.72% of the given dose were excreted in urine, feces and bile, respectively. The metabolites of the vitexin were hydrolyzed via deglycosylation. The pharmacokinetics of dogs after intravenous administration revealed t1/2, AUC0-∞ and mean residence time (MRT0-∞) values of 20.43±6.37 min, 227.96±26.68 mg•min/L and 17.12±4.33 min, respectively. The no-observed-adverse-effect level (NOAEL) was 50 mg/kg body weight/day. There was no significant accumulation effect at 8 or 20 mg/kg/day in dogs over 92 days of repeated administration. For the 50 mg/kg/day dose group, the exposure (AUC, Cmax) decreased significantly with prolonged administration. This trend suggests that repeated administration accelerates vitexin metabolism. Conclusion: The absorption of vitexin following routine oral administration was very low. To improve the bioavailability of vitexin, the development of an injectable formulation would be a suitable alternative choice.

Effects of pronounced haemodilution on the plasma protein binding of lidocaine

Perfusion ◽  
1995 ◽  
Vol 10 (1) ◽  
pp. 17-20 ◽  
Author(s):  
PA Lönnqvist ◽  
L. Herngren
Keyword(s):  
Plasma Concentration ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Free Fraction ◽  
Total Plasma ◽  
Free Concentration ◽  
Significant Difference ◽  
Total Plasma Concentration ◽  
Pharmacologically Active

The effects of pronounced haemodilution on the protein binding of lidocaine was investigated in vitro in plasma from five healthy adult volunteers. The plasma was diluted with a phosphate buffer to reach a plasma protein concentration normally seen during paediatric cardiopulmonary bypass (CPB) and protein binding was determined at a low (1.5 μg/ml) and a moderate (4 μg/ml) total plasma concentration of lidocaine. The effects of different haematocrits on plasma protein binding was also determined over the haematocrit range 20-60%. The binding of lidocaine was found to be inversely related to the degree of dilution, i.e. the free fraction increased significantly with increasing dilution (p < 0.0001). Furthermore, the binding was dependent on the total plasma concentration of lidocaine, since a significantly higher percentage of free drug was found at the higher total lidocaine level (4 μg/ml) compared with the lower level (1.5 μg/ml) (p < 0.05). No significant difference in the free fraction of lidocaine could be found over the studied haematocrit range. The results of the present study indicate that plasma protein levels commonly associated with CPB in neonates and infants are associated with a significant increase in the free, unbound and pharmacologically active fraction of lidocaine compared with normal conditions. The use of commonly recommended dosages of lidocaine might result in toxic-free concentration in this setting.

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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