The fatty acid content and drug binding characteristics of commercial albumin preparations

Birkett, Donald; Myers, Shirley P.; Sudlow, Gillian

doi:10.1016/0009-8981(78)90302-9

Cited by 39 publications

(19 citation statements)

References 6 publications

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“…Drug-endogenous Compound Interactions Drug binding can be modulated by simultaneous binding of endogenous compounds. Anions of long-chain fatty acids can at low ligand-to-protein molar ratios (Յ2 : 1), most probably allosterically, diminish binding of S(Ϫ)-and R(ϩ)-thiamylal, 56) diazepam, 21) L-tryptophan, 21) and dansylsarcosine 57,58) to site II. The effect on etodolac binding is dependent on the stereochemistry of the drug, because binding of the (R)-form was increased, whereas binding of the (S)-form was decreased.…”

Section: -3 Endogenous Compoundsmentioning

confidence: 99%

“…For site I ligands, the situation usually is different. At molar ratios of Յ3-4 : 1, anions of long-chain fatty acids increase binding of, for example, furosemide (in serum samples 60,61) ), warfarin, 21) DNSA, 57) and bilirubin. 21) In contrast, at molar ratios of Ն5-6 : 1, ligand binding is competitively diminished by the fatty acid anions.…”

Section: -3 Endogenous Compoundsmentioning

confidence: 99%

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Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

Kragh‐Hansen

Chuang

Otagiri

2002

Biological & Pharmaceutical Bulletin

910

776

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Recent work with approaches like recombinant mutants and X-ray crystallography has given much new information about the ligand-binding properties of human serum albumin (HSA). The information increases the understanding of this unique transport and depot protein and could give a structural basis for the possible construction of therapeutic agents with altered HSA-binding properties. A tabulation of high-affinity binding sites for both endogenous and exogenous compounds has been made; it could be useful for the above-mentioned purpose, but it could also be of value when trying to predict potential drug interactions at the protein-binding level. Drug displacement is not always a complication to therapy; it can be used to increase the biological effect of a drug. However, due to rebinding at other sites, the increase in the free concentration of a displaced ligand can be less than expected. Drugs and drug metabolites can also interact covalently with HSA; thiol-containing drugs often bind to the single free cysteine residue of HSA, and glucuronidated drugs react irreversibly with other residues of the protein. Reversible binding of ligands is often stereospecific, and therefore immobilized HSA can be used to separate drug isomers. Albumin-containing dialysates are useful for extracorporeal removal of endogenous toxins and in the treatment of drug overdoses. HSA has different types of hydrolytic activities, which also can be stereospecific. The esterase-like property seems especially useful in converting prodrugs to active drugs in plasma.

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Section: -3 Endogenous Compoundsmentioning

confidence: 99%

Section: -3 Endogenous Compoundsmentioning

confidence: 99%

Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

Kragh‐Hansen

Chuang

Otagiri

2002

Biological & Pharmaceutical Bulletin

910

776

View full text Add to dashboard Cite

show abstract

“…The increases in the unbound fraction of warfarin enantiomers that were bound to fatty acid-free HSA by adding ethanol differed from that to proteins in commercial albumin preparations. It was reported that NEFA affects the binding of warfarin to HSA, [18][19][20] and that NEFA in commercial albumin preparations affected the binding of probes to Site I. 21) Hence, it is considered that NEFA may affect the effects of ethanol on the unbound fraction of warfarin.…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that NEFA affects the binding of warfarin to HSA, [18][19][20] and that NEFA in commercial albumin preparations affected the binding of probes to Site I. 21) Hence, it is considered that NEFA may affect the effects of ethanol on the unbound fraction of warfarin. The concentration of NEFA in human plasma is 0.1-2 mEq/l.…”

Section: Discussionmentioning

confidence: 99%

Effect of Ethanol on the Binding of Warfarin Enantiomers to Human Serum Albumin

Tatsumi

Kadobayashi

Iwakawa

2007

Biological & Pharmaceutical Bulletin

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Ethanol is widely used as a pharmaceutical excipient for the solubilization of many hydrophobic drugs for injections. However, there are only few studies about drug interaction with pharmaceutical excipients in the body after injection. In this study, the effect of ethanol (500 mM) or several alcohols (500 mM) on the stereoselective binding of warfarin enantiomers to fatty acid-free human serum albumin (HSA) or proteins of commercial albumin preparations was investigated. An ultrafiltration method was used for the separation of unbound warfarin enantiomers. By the addition of ethanol or 1-propanol, the unbound fraction of the S-enantiomer was decreased. On the other hand, the unbound fraction of the R-enantiomer was increased by the addition of ethanol or 1-propanol. Unbound fractions of both the S-and R-enantiomer were decreased by 2-propanol. In various commercial albumin preparations, unbound fractions of both the S-and R-enantiomer were increased by ethanol. The different effects of ethanol among fatty acid-free HSA and commercial albumin preparations were observed.

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“…We tentatively attribute the exogenous albumin-mediated reduction of DCI to the binding of the fluorescein moiety of fluorescein-DFO to one of purified-albumin's hydrophobic binding sites, leading to a partial loss of sensitivity to quenching of the fluorescent chelator by iron. As the majority of such sites is normally occupied in plasma [28], their interference with the above assay should be minor. Effect of chelators on DCI, LPI, and eLPI measurements NTBI is considered a primary target of chelators and has been used as an indicator of chelator efficacy [18].…”

Section: Effect Of Serum Components On Lpi and Elpimentioning

confidence: 99%

Non‐transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients

Breuer¹,

Ghoti

Shattat³

et al. 2011

American J Hematol

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Non-transferrin bound iron (NTBI) is commonly detected in patients with systemic iron overload whose serum iron-binding capacity has been surpassed. It has been perceived as an indicator of iron overload, impending organ damage and a chelation target in poly-transfused thalassemia patients. However, NTBI is a heterogeneous entity comprising various iron complexes, including a significant redox-active and readily chelatable fraction, which we have designated as ''labile plasma iron'' (LPI). We found that LPI levels can be affected by plasma components such as citrate, uric acid, and albumin. However, the inclusion of a mild metal mobilizing agent in the LPI assay (designated here as ''eLPI''), at concentrations that do not affect transferrin-bound iron, largely overcomes such effects and provides a measure of the full NTBI content. We analyzed three distinct groups of poly-transfused, iron overloaded thalassemia patients: non-chelated children (3-13 yrs, Gaza, Palestine), chelated adolescents-young adults (13-28 yrs, Israel), and chelated adults (27-61 yrs, Israel) for LPI and eLPI. The eLPI levels in all three groups were roughly commensurate (r 2 5 0.61-0.75) with deferrioxamine-detectable NTBI, i.e., DCI. In older chelated patients, eLPI levels approximated those of LPI, but in poly-transfused unchelated children eLPI was notably higher than LPI, a difference attributed to plasma properties affected by labile iron due to lack of chelation, possibly reflecting age-dependent attrition of plasma components. We propose that the two formats of NTBI measurement presented here are complementary and used together could provide more comprehensive information on the forms of NTBI in patients and their response to chelation. Am. J. Hematol. 87:55-61, 2012. V

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The fatty acid content and drug binding characteristics of commercial albumin preparations

Cited by 39 publications

References 6 publications

Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

Effect of Ethanol on the Binding of Warfarin Enantiomers to Human Serum Albumin

Non‐transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients

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