Impact of Changes in Free Concentrations and Drug-Protein Binding on Drug Dosing Regimens in Special Populations and Disease States

Celestin, Marie N.; Musteata, Florin Marcel

doi:10.1016/j.xphs.2021.05.018

Cited by 26 publications

(18 citation statements)

References 49 publications

(119 reference statements)

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“…The drug–protein interaction with bloodstream, serum, and plasma may cause the formation of a drug–protein complex that greatly influences the distribution, toxicity, and metabolism of drugs in the body. l -Ascorbic acid (LAA) transports various substances like bilirubin, fatty acids, metal ions, hormones, and exogenous drugs and functions mainly as a carrier protein for steroid and thyroid hormones that play a major role in stabilizing extracellular fluid volume by contributing to the oncotic pressure (colloid osmotic pressure) of plasma and in a class of mammals with diverse functions in the transportation of substances and the metabolism and distribution of exogenous and endogenous molecules . Bovine serum albumin (BSA) is mainly selected as an adequate protein model for drug–protein interaction due to its low cost, availability, morphological resemblance with human serum albumin, and high bonding sites to metal complexes …”

Section: Introductionmentioning

confidence: 99%

One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

et al. 2021

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The physicochemical approaches and biological principles in bio-nanotechnology favor specially functionalized nanosized particles. Cuprous oxide nanoparticles (β-Cu2O NPs) of cuprite phase with a little tenorite (CuO) may be very effective in the development of novel therapeutic approaches against several fatalities including A-549 lung carcinoma cell lines. Consequently, the synthesis of β-Cu2O NPs for the improvement in the therapeutic index and drug delivery application is becoming an effective strategy in conventional anticarcinoma treatment. Hence, surface-enhanced nanosized spherical cuprous oxide nanoparticles (β-Cu2O NPs) of cuprite phase were successfully prepared using poly(ethylene glycol) (PEG) as an amphiphilic nonionic surfactant and l-ascorbic acid (K3[Cu(Cl5)]@LAA-PEG) reduced to cuprites β-Cu2O NPs via the sonochemical route. Less improved toxicity and better solubility of β-Cu2O NPs compared with Axitinib were a major reason for producing β-Cu2O NPs from K3[Cu(Cl5)]@LAA-PEG (LAA, l-ascorbic acid, PEG, poly(ethylene glycol) (PEG)). These nanoparticle syntheses have been suggested to influence their cytotoxicity, free-radical scavenging analysis, and reactive oxygen species (ROS) using poly(ethylene glycol) (PEG) and l-ascorbic acid (LAA) as coated and grafted materials due to their dose-dependent nature and IC50 calculations. The surface morphology of the formed β-Cu2O NPs has been examined via UV–vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy with energy diffraction scattering spectroscopy (SEM@EDS), field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) analysis. X-ray diffraction (XRD) and Brunauer–Emmett–Teller (BET) surface analysis results confirm the presence of pure cuprite with a very little amount of tenorite (CuO) phase, Dynamic light scattering (DLS) confirms the negative ζ-value with stable nature. Docking was performed using PDB of lung carcinomas and others, as rigid receptors, whereas the β-Cu2O NP cluster was treated as a flexible ligand.

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Section: Introductionmentioning

confidence: 99%

One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

et al. 2021

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“…In vivo, drug molecules are either bound to plasma or tissue proteins, or in an unbound/free state. Moreover, PPB properties greatly vary between drugs [ 15 , 16 ]. Since bound drugs are too large to penetrate most biological membranes, only unbound fractions can enter the target tissue and exert the expected pharmacological effect.…”

Section: Protein Binding: General Principlesmentioning

confidence: 99%

“…Several proteins are involved in the protein binding of antibiotics including plasm proteins, extracellular tissue proteins and/or intracellular tissue proteins. In vivo, dru molecules are either bound to plasma or tissue proteins, or in an unbound/free stat Moreover, PPB properties greatly vary between drugs [15,16]. Since bound drugs are to large to penetrate most biological membranes, only unbound fractions can enter the targ tissue and exert the expected pharmacological effect.…”

Section: Protein Binding: General Principlesmentioning

confidence: 99%

Protein Binding in Translational Antimicrobial Development-Focus on Interspecies Differences

2022

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Background/Introduction: Plasma protein binding (PPB) continues to be a key aspect of antibiotic development and clinical use. PPB is essential to understand several properties of drug candidates, including antimicrobial activity, drug-drug interaction, drug clearance, volume of distribution, and therapeutic index. Focus areas of the review: In this review, we discuss the basics of PPB, including the main drug binding proteins i.e., Albumin and α-1-acid glycoprotein (AAG). Furthermore, we present the effects of PPB on the antimicrobial activity of antibiotics and the current role of PPB in in vitro pharmacodynamic (PD) models of antibiotics. Moreover, the effect of PPB on the PK/PD of antibiotics has been discussed in this review. A key aspect of this paper is a concise evaluation of PPB between animal species (dog, rat, mouse, rabbit and monkey) and humans. Our statistical analysis of the data available in the literature suggests a significant difference between antibiotic binding in humans and that of dogs or mice, with the majority of measurements from the pre-clinical species falling within five-fold of the human plasma value. Conversely, no significant difference in binding was found between humans and rats, rabbits, or monkeys. This information may be helpful for drug researchers to select the most relevant animal species in which the metabolism of a compound can be studied for extrapolating the results to humans. Furthermore, state-of-the-art methods for determining PPB such as equilibrium dialysis, ultracentrifugation, microdialysis, gel filtration, chromatographic methods and fluorescence spectroscopy are highlighted with their advantages and disadvantages.

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“…It is well‐accepted that the pharmacological activity of antibiotics depends on the free or unbound concentration of the drug at the site of infection (Celestin & Musteata, 2021). Plasma protein binding rate (PPBR) is a critical parameter for predicting of free concentration of drugs in tissues.…”

Section: Introductionmentioning

confidence: 99%

Determination of doxycycline’s plasma protein binding rates in the plasma of grass carp ( Ctenopharyngodon idella ), yellow catfish ( Pelteobagrus fulvidraco ) and crayfish ( Procambarus clarkii ) by an ultrafiltration method at different temperatures with different concentrations

Sun

Chang

et al. 2022

Aquaculture Research

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The objective of this study was to compare the plasma protein binding rates (PPBRs) of doxycycline (DC) in the plasma of grass carp (Ctenopharyngodon idella), yellow catfish (Pelteobagrus fulvidraco) and crayfish (Procambarus clarkii) at different temperatures (4, 18 and 25℃) with different concentrations (1, 5, 10 and 20 μg/ml). A rapid and simple method of ultrafiltration (UF) was employed to determine the PPBR of DC in the plasma. The results showed that PPBRs were increased with the rise of the concentration of DC at the same temperature. At 4 ℃, PPBRs were increased from 90.00% to 99.51%, 89.81% to 98.71% and 84.08% to 99.21% in the plasma of grass carp, yellow catfish and crayfish respectively. At 18℃ and 25℃, the same trend was also presented in the three species. Meanwhile, PPBRs of DC might have the atypical nonlinear phenomenon. Otherwise, the temperature could affect the PPBR of DC at a certain degree in the plasma of grass carp and yellow catfish at the same concentration of DC. However, no regularity was presented in the plasma of crayfish. Overall, the increased concentration of DC significantly affected the PPBR in the plasma of grass carp, yellow catfish and crayfish at the same temperature, but the temperature only had a certain influence on the PPBR of grass carp and yellow catfish. Hence, this study is beneficial to design suitable therapeutic regimens and formulations of DC in grass carp, yellow catfish and crayfish at different temperatures.

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Impact of Changes in Free Concentrations and Drug-Protein Binding on Drug Dosing Regimens in Special Populations and Disease States

Cited by 26 publications

References 49 publications

One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

Protein Binding in Translational Antimicrobial Development-Focus on Interspecies Differences

Determination of doxycycline’s plasma protein binding rates in the plasma of grass carp ( Ctenopharyngodon idella ), yellow catfish ( Pelteobagrus fulvidraco ) and crayfish ( Procambarus clarkii ) by an ultrafiltration method at different temperatures with different concentrations

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Impact of Changes in Free Concentrations and Drug-Protein Binding on Drug Dosing Regimens in Special Populations and Disease States

Cited by 26 publications

References 49 publications

One-Pot Surface Modification of β-Cu2O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

One-Pot Surface Modification of β-Cu2O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

Protein Binding in Translational Antimicrobial Development-Focus on Interspecies Differences

Determination of doxycycline’s plasma protein binding rates in the plasma of grass carp ( Ctenopharyngodon idella ), yellow catfish ( Pelteobagrus fulvidraco ) and crayfish ( Procambarus clarkii ) by an ultrafiltration method at different temperatures with different concentrations

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One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis

One-Pot Surface Modification of β-Cu₂O NPs for Biocatalytic Performance against A-549 Lung Carcinoma Cell Lines through Docking Analysis