Effects of Phenylbutazone, Tolbutamide, and Clofibric Acid on Binding of Racemic Warfarin and Its Enantiomers to Human Serum Albumin

Veronich, Karen; White, George L.; Kapoor, A.

doi:10.1002/jps.2600681213

Cited by 22 publications

(6 citation statements)

References 33 publications

(10 reference statements)

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“…It is not always easy to identify the reasons why data from different methods disagree. Larger than normal variations can be noted between the binding parameters reported for warfarin-HSA in phosphate buffer (Table II) (5)(6)(7)(8)(9). The binding parameters for the warfarin-HSA primary site determined under similar conditions are in reasonable agreement.…”

Section: Comparison Of Binding Parameters From Differentmentioning

confidence: 94%

“…0003-2700/90/0362-2114$02.50/0 Binding of warfarin to human serum albumin (HSA) is a classical example of a multiclass model which has been studied by a variety of methods, yet comparisons of reported results illustrate inconsistencies (5)(6)(7)(8)(9). Warfarin is an anticoagulant which decreases prothrombinogenic activity by inhibiting the vitamin K cycle (10).…”

Section: Introductionmentioning

confidence: 99%

“…If the protein concentration was diluted by a factor of 3, then the n values would be one-third of that expected, based on the sample protein concentration. It is well established for warfarin-HSA primary binding that rtx equals one (5)(6)(7)(8)(9). The modified Hummel-Dreyer method produces the same results (Table I), thus the on-column dilution of protein is of no consequence.…”

Section: Introductionmentioning

confidence: 99%

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Determination of warfarin-human serum albumin protein binding parameters by an improved Hummel-Dreyer high-performance liquid chromatographic method using internal surface reversed-phase columns

Pinkerton¹,

Koeplinger²

1990

Anal. Chem.

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The Hummel-Dreyer size-exclusion high-performance liquid chromatographic method for the determination of protein binding parameters has been improved and automated by use of an internal surface reversed-phase (ISRP) column (5 cm X 4.6 mm) and a computer-controlled mobile-phase delivery system with low volume syringe mixing. The high-efficiency ISRP columns, which are nonadsorptive and exclusionary to serum proteins but allow partitioning of small molecules with an internal peptide bonded phase, maintain high performance after many injections of human serum albumin (HSA), enable the use of short columns, and provide for the resolution of primary ligand from protein binding displacers. The modified Hummel-Dreyer high-performance liquid chromatographic method was demonstrated by the determination of binding parameters for warfarin-HSA in phosphate buffer, which were found to be n1 = 1.0, n2 = 2.1, K1 = 3.30 X 10(5) M-1, and K2 = 2.03 X 10(4) M-1. The necessary sequence of chromatographic experiments was repeated 4 times at 18 separate warfarin mobile phase concentrations. Each automated sequence required 8 h to complete. The parameters were measured with a precision of less than 10% relative standard deviation.

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Section: Comparison Of Binding Parameters From Differentmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Determination of warfarin-human serum albumin protein binding parameters by an improved Hummel-Dreyer high-performance liquid chromatographic method using internal surface reversed-phase columns

Pinkerton¹,

Koeplinger²

1990

Anal. Chem.

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“…Metabolites by Phenglbutazone Phenylbutazone and many other drugs bind to the same site on albumin as the coumarin anticoagulants. [17][18][19] Although no longer used in the clinic, phenylbutazone serves as an interesting tool to investigate the mechanism of warfarin metabolite binding. In the presence of 100 mghter phenylbutazone the mean (fSD) percent unbound in plasma increased from 1.08 +-0.07 to 2.37 f 0.22 for (R,S)-warfarin alcohol and from 4.12 f 0.24 to 9.18 2 1.14 for (S)-7-hydroxywarfarin.…”

Section: Displacement Of Warfarin Enantiomers Andmentioning

confidence: 99%

Warfarin metabolites: Stereochemical aspects of protein binding and displacement by phenylbutazone

1993

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The in vitro human serum albumin binding characteristics of the enantiomers of the major metabolites of warfarin [6-hydroxywarfarin (6-HW), 7-hydroxywarfarin (7-HW), (S)-warfarin alcohols [(S,S)- and (S,R)-WA], and (R,S)-warfarin alcohol [(R,S)-WA]] have been studied, using a stereospecific HPLC assay. Warfarin metabolites are less bound both within plasma and a 40 g/liter solution of human serum albumin than the enantiomers of warfarin. The reduced warfarin metabolites have a lower fraction unbound [1.33% for (S,R)-WA, 2.09% for (S,S)-WA, and 1.04% for (R,S)-WA] than hydroxylated metabolites [3.24% for (R)-6-HW, 4.26% (S)-6-HW, 4.49% for (R)-7-HW and 4.27% for (S)-7-HW] to HSA. Phenylbutazone produced a concentration-dependent increase in the unbound fraction of all metabolites. It was possible to predict the unbound fraction of warfarin metabolites based on the unbound fraction of warfarin enantiomers.

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“…Figure 7. Distribution of the number of studies of binding with human serum albumin by the value of the obtained molarity-based association constant for (a) indomethacine[37][38][39][40][41][42][43][44][45][46][47], (b) phenylbutazone[27,28,37,[48][49][50][51][52][53][54][55][56], (c) quercetin[38,[57][58][59][60][61][62][63][64][65][66][67][68][69][70], (d) warfarin[53,56,[71][72][73][74][75][76][77][78][79][80]…”

mentioning

confidence: 99%

Binding Constants of Clinical Drugs and Other Organic Ligands with Human and Mammalian Serum Albumins

2021

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A dataset containing the experimental values of the equilibrium binding constants of clinical drugs, and some other organic ligands with human and mammalian (predominantly bovine) serum albumins, is assembled. The affinity of drugs to albumin governs their pharmacokinetic properties, related to permeability through physiological barriers and distribution within the organism. The dataset contains 1755 records gathered from 346 original literature sources describing the albumin affinity of 324 different substances. The data were extracted from both articles and existing protein-binding databases applied strict data selection rules in order to exclude the values influenced by the third-party compounds. The dataset provides the details on the experimental conditions of the measurements, such as temperature; protein and ligand concentrations; buffer pH, composition and concentration; and the method and model used for the binding constant calculations. Analysis of the data reveals discrepancies between the values from different studies, as well as the significant influence of the measurement method. Averaging the values from multiple independent measurements from the dataset may help to determine the reliable values of the binding constants. The dataset can be used as the reference dataset for the development of predictive models to calculate binding constants, and as the choice for the experimental setup in the future albumin-binding studies.

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Effects of Phenylbutazone, Tolbutamide, and Clofibric Acid on Binding of Racemic Warfarin and Its Enantiomers to Human Serum Albumin

Cited by 22 publications

References 33 publications

Determination of warfarin-human serum albumin protein binding parameters by an improved Hummel-Dreyer high-performance liquid chromatographic method using internal surface reversed-phase columns

Determination of warfarin-human serum albumin protein binding parameters by an improved Hummel-Dreyer high-performance liquid chromatographic method using internal surface reversed-phase columns

Warfarin metabolites: Stereochemical aspects of protein binding and displacement by phenylbutazone

Binding Constants of Clinical Drugs and Other Organic Ligands with Human and Mammalian Serum Albumins

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