The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches

Obradović, Darija; Radan, Milica; Đikić, Teodora; Nikolić, Marija Popović; Oljačić, Slavica; Nikolić, Katarina

doi:10.1016/j.jpba.2022.114593

Cited by 11 publications

(7 citation statements)

References 26 publications

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“…Among the tested drugs, pethidine binds mainly to α1-acid glycoprotein and the rest bind mainly to albumin [ 88 , 93 , 94 , 95 , 96 , 97 , 98 , 99 ] (no data on binding protein for temocapril, so binding to albumin was assumed based on pka < 7.4, acidic). The free fraction of drugs in patient plasma was estimated using Equation (3) [ 21 ]:

where f u,p,CI , f u,p,HT , P prot,CI and P prot,HT represent the unbound fraction of the drug in the plasma of patients and healthy subjects and the concentration of drug-bound proteins in the plasma of patients and healthy subjects, respectively.…”

Section: Methodsmentioning

confidence: 99%

Simultaneously Predicting the Pharmacokinetics of CES1-Metabolized Drugs and Their Metabolites Using Physiologically Based Pharmacokinetic Model in Cirrhosis Subjects

Luo,

Zhang,

et al. 2024

Pharmaceutics

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Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aimed to develop a semi-physiologically based pharmacokinetic (semi-PBPK) model to simultaneously predict the pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis (LC) patients. Six prodrugs (enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. Parameters such as organ blood flows, plasma-binding protein concentrations, functional liver volume, hepatic enzymatic activity, glomerular filtration rate (GFR) and gastrointestinal transit rate were integrated into the simulation. The pharmacokinetic profiles of these drugs and their active metabolites were simulated for 1000 virtual individuals. The developed semi-PBPK model, after validation in healthy individuals, was extrapolated to LC patients. Most of the observations fell within the 5th and 95th percentiles of simulations from 1000 virtual patients. The estimated AUC and Cmax were within 0.5–2-fold of the observed values. The sensitivity analysis showed that the decreased plasma exposure of active metabolites due to the decreased CES1 was partly attenuated by the decreased GFR. Conclusion: The developed PBPK model successfully predicted the pharmacokinetics of CES1 substrates and their metabolites in healthy individuals and LC patients, facilitating tailored dosing of CES1 substrates in LC patients.

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Section: Methodsmentioning

confidence: 99%

Simultaneously Predicting the Pharmacokinetics of CES1-Metabolized Drugs and Their Metabolites Using Physiologically Based Pharmacokinetic Model in Cirrhosis Subjects

Luo,

Zhang,

et al. 2024

Pharmaceutics

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“…When the protein‐based stationary phases are used to measure plasma or tissue protein binding, it is important to convert the biomimetic chromatographic retention to binding constants or percentages of binding used by absorption, distribution, metabolism and toxicity scientists. It is also important to compare other in vitro methods 33 . It is worth highlighting the differences and similarities between various methods.…”

Section: New Applications and Modelsmentioning

confidence: 99%

“…It is also important to compare other in vitro methods. 33 It is worth highlighting the differences and similarities between various methods. The chromatographic methods are becoming more precise and differential for strongly bound compounds, unlike the equilibrium dialysis and ultrafiltration methods, which are less accurate at the higher binding range.…”

Section: New Applications and Modelsmentioning

confidence: 99%

“…The human plasma protein binding of drugs can reveal potential drug–drug interactions and influence the free concentration available at the target. The application of immobilised HSA and the α‐1‐acid glycoprotein phases is often used to reveal the structure and binding property relationships and aid the computational approach to drug design 33 . There have been efforts to immobilise various proteins on silica surfaces and to use them as stationary phases in what is called bioaffinity chromatography 34 .…”

Section: Introductionmentioning

confidence: 99%

“…The application of immobilised HSA and the α‐1‐acid glycoprotein phases is often used to reveal the structure and binding property relationships and aid the computational approach to drug design. 33 There have been efforts to immobilise various proteins on silica surfaces and to use them as stationary phases in what is called bioaffinity chromatography. 34 Several protein‐based stationary phases were synthesised for studying drug–protein interactions.…”

Section: Introductionmentioning

confidence: 99%

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Biomimetic chromatography—A novel application of the chromatographic principles

Valkó¹

2022

Analytical Science Advances

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Biomimetic chromatography is the name of the High Performance Liquid Chromatography (HPLC) methods that apply stationary phases containing proteins and phospholipids that can mimic the biological environment where drug molecules distribute. The applied mobile phases are aqueous organic with a pH of 7.4 to imitate physiological conditions that would be encountered in the human body. The calibrated retention of molecules on biomimetic stationary phases reveals a compound's affinity to proteins and phospholipids, which can be used to model the biological and environmental fate of molecules. This technology, when standardised, enables the prediction of in vivo partition and distribution behaviour of compounds and aids the selection of the best compounds for further studies to become a drug molecule. Applying biomimetic chromatographic measurements helps reduce the number of animal experiments during the drug discovery process. New biomimetic stationary phases, such as sphingomyelin and phosphatidylethanolamine, widen the application to the modelling of blood-brain barrier distribution and lung tissue binding. Recently, the measured properties have also been used to predict toxicity, such as phospholipidosis and cardiotoxicity. The aquatic toxicity of drugs and pesticides can be predicted using biomimetic chromatographic data. Biomimetic chromatographic separation methods may also be extended in the future to predict protein and receptor binding kinetics. The development of new biomimetic stationary phases and new prediction models will further accelerate the widespread application of this analytical method.

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An improved workflow for the development of MS-compatible liquid chromatography assay purity and purification methods by using automated LC Screening instrumentation and in silico modeling

Manheim,

Singh,

Aggarwal

et al. 2024

Anal Bioanal Chem

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The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches

Cited by 11 publications

References 26 publications

Simultaneously Predicting the Pharmacokinetics of CES1-Metabolized Drugs and Their Metabolites Using Physiologically Based Pharmacokinetic Model in Cirrhosis Subjects

Simultaneously Predicting the Pharmacokinetics of CES1-Metabolized Drugs and Their Metabolites Using Physiologically Based Pharmacokinetic Model in Cirrhosis Subjects

Biomimetic chromatography—A novel application of the chromatographic principles

An improved workflow for the development of MS-compatible liquid chromatography assay purity and purification methods by using automated LC Screening instrumentation and in silico modeling

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