Interaction of the Enantiomers of Warfarin with Human Serum Albumin, Peptides and Amino Acids

Miller, John; Smail, G.A.

doi:10.1111/j.2042-7158.1977.tb11501.x

Cited by 32 publications

(14 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an example, it has been demonstrated in many reports that the displacement effects and allosteric interactions seen on HSA columns are similar to those observed for soluble HSA [32,53–61]. Good agreement with values that have been determined by equilibrium dialysis and other solution-based methods has also been found in the equilibrium constants measured by HPAC for immobilized albumins and in the temperature dependence of these equilibrium constants, the associated changes in entropy and enthalpy, and the rate constants for solute-albumin systems that have been measured by HPAC [32,53,62–65]. …”

Section: Introductionsupporting

confidence: 82%

Characterization of drug–protein interactions in blood using high‐performance affinity chromatography

Hage

Jackson

Sobansky

et al. 2009

J of Separation Science

144

View full text Add to dashboard Cite

The binding of drugs with proteins in blood, serum or plasma is an important process in determining the activity, distribution, rate of excretion, and toxicity of drugs in the body. Highperformance affinity chromatography (HPAC) has received a great deal of interest as a means for studying these interactions. This review examines the various techniques that have been used in HPAC to examine drug-protein binding and discusses the types of information that can be obtained through this approach. A comparison of these techniques with traditional methods for binding studies (e.g., equilibrium dialysis and ultrafiltration) will also be presented. The use of HPAC with specific serum proteins and binding agents will then be discussed, including human serum albumin and α 1 -acid glycoprotein. Several examples from the literature are provided to illustrate the applications of such research. Recent developments in this field are also described, such as the use of improved immobilization techniques, new data analysis methods, techniques for working for directly with complex biological samples, and work with immobilized lipoproteins. The relative advantages and limitations of the methods that are described will be considered and the possible use of these techniques in the high-throughput screening or characterization of drugprotein binding will be discussed.

show abstract

Section: Introductionsupporting

confidence: 82%

Characterization of drug–protein interactions in blood using high‐performance affinity chromatography

Hage

Jackson

Sobansky

et al. 2009

J of Separation Science

144

View full text Add to dashboard Cite

show abstract

“…As an example, literature values for the association equilibrium constants between HSA and R-warfarin in pH 7.4, 0.067 M phosphate buffer have ranged from (2.1 to 3.3) × 10 5 M −1 at 37 • C [10,20,[33][34][35][36]. Part of the variation in these numbers may be due to differences in the experimental errors of the various techniques used in these studies (i.e., zonal elution [10,20,33], equilibrium dialysis [35,36], and frontal analysis [34]). However, the results of this report suggest that part of this variation could also be a result of differences in the way the warfarin solutions were used and stored in these studies.…”

Section: Effects Of Warfarin Stability On Protein Bindingmentioning

confidence: 99%

Stability of warfarin solutions for drug–protein binding measurements: Spectroscopic and chromatographic studies

Moser

Kingsbury

Hage

2006

Journal of Pharmaceutical and Biomedical Analysis

View full text Add to dashboard Cite

Warfarin is commonly used in drug-protein binding studies as a displacement marker for Sudlow site I on the protein human serum albumin (HSA). This study examined the stability of aqueous warfarin solutions prepared for such experiments. This was investigated using NMR spectroscopy and affinity chromatography. It was found by 1H NMR that warfarin underwent a slow first-order conversion in aqueous solution. The rate of this reaction increased with temperature, giving rate constants at pH 7.4 of 0.0086 h(-1) at 25 degrees C and 0.041 h(-1) at 37 degrees C. It was concluded from further 1H and 13C NMR studies, along with molecular modeling, that this process involved the conversion of the minor cyclic hemiketal form of warfarin to its major cyclic hemiketal. This reaction had a small but measurable effect on the binding of R- and S-warfarin to HSA, as demonstrated by HPLC using an immobilized HSA affinity column. From this work, general guidelines were developed concerning the usable lifetimes for warfarin that is prepared in aqueous solutions for studies of drug-protein binding.

show abstract

“…Warfarin is bound to site I and S-form binding appears to be of a greater extent than R-form binding (Miller & Smail 1977;Toon & Trager 1984). Likewise, different oxazepam esters show preferential binding of the S(+) form to site II (Fitos et al 1983).…”

mentioning

confidence: 95%

Protein Binding and Stereoselectivity of Nonsteroidal Anti-Inflammatory Drugs

Lapicque¹,

Muller²,

Payan³

et al. 1993

Clinical Pharmacokinetics

View full text Add to dashboard Cite

Stereoselective binding of nonsteroidal anti-inflammatory drugs (NSAIDs) can be studied using various techniques. Thus the results obtained by different investigators may be poorly consistent and even contradictory. NSAIDs are bound stereoselectively to serum albumin to different degrees depending on the drug investigated (ibuprofen, indoprofen, carprofen, etodolac, ketoprofen and flurbiprofen). For other drugs, both enantiomers are bound to a similar extent (pirprofen, fenoprofen). This stereoselectivity could vary with experimental conditions, in particular with protein concentration (ketoprofen, etodolac), leading to individual differences. Finally, the stereoselectivity of protein binding and of pharmacokinetics can be compared: differences in binding between enantiomers can explain their differences in pharmacokinetics, once metabolic properties such as inversion have been taken into account.

show abstract

Interaction of the Enantiomers of Warfarin with Human Serum Albumin, Peptides and Amino Acids

Cited by 32 publications

References 3 publications

Characterization of drug–protein interactions in blood using high‐performance affinity chromatography

Characterization of drug–protein interactions in blood using high‐performance affinity chromatography

Stability of warfarin solutions for drug–protein binding measurements: Spectroscopic and chromatographic studies

Protein Binding and Stereoselectivity of Nonsteroidal Anti-Inflammatory Drugs

Contact Info

Product

Resources

About