Chromatographic analysis of allosteric effects between ibuprofen and benzodiazepines on human serum albumin

Chen, Jianzhong; Fitos, Ilona; Hage, David S.

doi:10.1002/chir.20216

Cited by 25 publications

(30 citation statements)

References 33 publications

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“…Moreover, this methodology allows the study of the enantioselective protein-binding phenomena as well as enantiomer-enantiomer or chiral drugdrug interactions which are difficult to evaluate by conventional methods since they require the determination of the isomeric composition of the equilibrium mixture, i.e. by the use of pseudoracemates or enantioselective chromatographic techniques (Oravcová et al, 1996;Shibukawa et al, 1995;Fitos et al, 1999;Chen and Hage, 2004;Chen et al, 2006).…”

Section: Chromatographic and Electrophoretic Techniquesmentioning

confidence: 99%

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Microseparation techniques for the study of the enantioselectivity of drug–plasma protein binding

Escuder-Gilabert

Martínez-Gómez

Villanueva-Camañas

et al. 2008

Biomedical Chromatography

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Stereoselectivity in protein binding can have a significant effect on the pharmacokinetic and pharmacodynamic properties of chiral drugs. The investigation of enantioselectivity of drugs in their binding with human plasma proteins and the identification of the molecular mechanisms involved in the stereodiscrimination by the proteins represent a great challenge for clinical pharmacology. In this review, the separation techniques used for enantioselective protein binding experiments are described and compared. An overview of studies on enantiomer-protein interactions, enantiomer-enantiomer interactions as well as chiral drug-drug interactions, including allosteric effects, is presented. The contribution of individual plasma proteins to the overall enantioselective binding and the animal species variability in drug-plasma protein binding stereoselectivity are reviewed.

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Section: Chromatographic and Electrophoretic Techniquesmentioning

confidence: 99%

“…The effects of (R)-and (S)-ibuprofen on the binding of benzodiazepines to HSA were also examined by biointeraction chromatography (Chen et al, 2006). The authors developed a general model to describe the binding of HSA to benzodiazepines and ibuprofen.…”

Section: Human Serum Albumin Studiesmentioning

confidence: 99%

Microseparation techniques for the study of the enantioselectivity of drug–plasma protein binding

Escuder-Gilabert

Martínez-Gómez

Villanueva-Camañas

et al. 2008

Biomedical Chromatography

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“…Such an approach has already been successfully utilized in examining a number of drug-drug interactions on HSA, including positive and negative allosteric effects as well as direct competition. 6,17 One current limitation of this method is it can only be applied to compounds that have at least a moderate solubility in aqueous buffers (i.e., solubilities of at least μM levels). This feature is needed to place enough of the injected compound in solution for detection and to have a sufficiently high concentration of the second solute in the mobile phase to produce a measurable shift in retention.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Studies of Allosteric Effects by Biointeraction Chromatography: Analysis of Protein Binding for Low-Solubility Drugs

Chen

Hage

2006

Anal. Chem.

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A new chromatographic method was developed for characterizing allosteric interactions between an immobilized binding agent and low solubility compounds. This approach was illustrated by using it to characterize the interactions between tamoxifen and warfarin during their binding to the protein human serum albumin (HSA), with β-cyclodextrin being employed as a solubilizing agent for these drugs. It was confirmed in this work through several experiments that warfarin had a single binding site on HSA with an association equilibrium constant of 2-5 × 10 5 M -1 (average, 3.9 × 10 5 M -1 ) at 37°C, in agreement with previous reports. It was also found that tamoxifen had a single major binding site on HSA, with an association equilibrium constant of 3-4 × 10 7 M -1 (average, 3.5 × 10 7 M -1 ) at 37°C. When warfarin was used as a mobile phase additive in competition studies with tamoxifen, this had a positive allosteric effect on tamoxifen/HSA binding, giving a coupling constant of 2.3 (± 0.3). Competitive studies using tamoxifen as a mobile phase additive indicated that tamoxifen had a negative allosteric effect on warfarin/HSA binding, providing a coupling constant of 0.79 (± 0.03). A unique feature of the technique described in this report was its ability to independently examine both directions of the warfarin/tamoxifen allosteric interaction. This approach is not limited to warfarin, tamoxifen and HSA but can also be used to study other solutes and binding agents.

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“…This may be because both the caprypate and diazepam ligands bind to multiple sites on the protein. The secondary bindings may cause allosteric interactions (30) to cause deviations in the E app values. In addition, the remaining HSAcaprylate type complex present was due to the fact that diazepam cannot fully replace the caprylate ligand.…”

Section: Thermal Energetics Of Hsa-drug Complexesmentioning

confidence: 99%

Assessment of the Dissociation Energetics of Some Selected Ligand Drugs Bound on Human Serum Albumin by Differential Scanning Calorimetry

Faroongsarng

2015

AAPS PharmSciTech

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Abstract. Drug-protein binding may play a role in the thermal energetics of protein denaturation and could lead to the determination of its equilibrium dissociation parameter. The aim of this study was to assess the energetics of a drug that was bound to human serum albumin (HSA) during thermal denaturation. Drugs that were bound at a single high-affinity primary binding site on HSA, including diazepam and ibuprofen, were employed. Commercial HSA was treated with charcoal to remove stabilizers and adjusted to 20% w/v in a pH 7.4 buffered solution. Serial concentrations of individual drugs up to 0.16 mmole/g-protein were added to the cleaned HSA solutions whereas diazepam was added to a commercial HSA solution. Samples were subjected to differential scanning calorimetry (DSC) set to run from 37 to 90°C at 3.0°C/min. Binding of the drug slightly increased the denaturing temperature of the cleaned HSA due to a shift in the equilibrium toward the native protein bound with the drug. Diazepam depressed the denaturing temperature of the commercial HSA by competing with the stabilizers already bound to the primary site of the HSA. This yielded not only the HSA-stabilizer but also the HSAdiazepam type complexes that exhibited a different denaturation process. A rational approximation of the Lumry-Eyring protein denaturation model was used to treat the DSC endotherms. The approximated scheme: N → k 3 K P was successfully fitted to the data. It was used to determine the dissociation parameters for diazepam and ibuprofen bound to the HSA. These results were comparable to those obtained from other methods.

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Chromatographic analysis of allosteric effects between ibuprofen and benzodiazepines on human serum albumin

Abstract: The effects of (R)-and (S

Cited by 25 publications

References 33 publications

Microseparation techniques for the study of the enantioselectivity of drug–plasma protein binding

Microseparation techniques for the study of the enantioselectivity of drug–plasma protein binding

Quantitative Studies of Allosteric Effects by Biointeraction Chromatography: Analysis of Protein Binding for Low-Solubility Drugs

Assessment of the Dissociation Energetics of Some Selected Ligand Drugs Bound on Human Serum Albumin by Differential Scanning Calorimetry

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