Human serum albumin drugs that bind

Sulfaphenazole (684) and sulfazamet (685) are both examples of relatively short acting sulfonamides (B-80MI40406) and their antibacterial activity has been tested against Escherichia coli, the former being more effective than the latter. Sulfaphenazole also displaces sulfonyl ureas from protein binding sites on human serum albumin and consequently increases the concentration of the free (active) drug and produces a more intense reaction that may result in hypoglycemia. 

A report on the binding of the anesthetic propofol to human serum albumin and to plasma presents a dataset that challenges simple notions of equilibria [70]. The unbound fraction of propofol was found to increase sharply at low drug concentrations. The authors appear to have carefully eliminated possible artifacts. Explanations based on cooperative binding modes are discussed though no clear explanation emerges. 

Kraak et al. (38) reported the first ACE application to study drug binding to a plasma protein. They used the model system warfarin-human serum albumin (HSA) to compare the suitability of the Hummel-Dreyer, frontal analysis, and vacancy peak methods. A more methodologically intended paper from Erim and Kraak (39) used VACE to study the displacement of warfarin from bovine serum albumin (BSA) by furosemide and phenylbutazone. They concluded that VACE is especially suited to examining competitive properties of simultaneously administered compounds toward a given protein-drug system. 

The binding of sulfonamides to serum albumin is thought to strongly affect the pharmacokinetics of drug action, and therefore CD spectroscopy has been used to deduce the nature of the association mechanism [71]. It was found in this study that most of the drug compounds would exhibit induced CD upon binding to either human, bovine, or rabbit serum albumin, and that the particular lineshape of the chiroptical spectrum was determined by the structural details of the bound solute. 

Many compounds bind to human serum albumin (HSA), which significantly reduces their in vivo activity and hence their potential as a drug lead. The fragmentation method has recently been used to find analogs of diflusinal (29) that have a reduced affinity toward HSA... 

Etacrynic acid interacts with human serum albumin and modifies its binding properties (45). Since it binds to two binding sites on albumin, the benzodiazepine binding site and the warfarin binding site, it can displace drugs that bind at those sites (46). It competitively displaced 7-hydroxymethotrexate from its binding proteins in vitro (47). The clinical significance of this effect is not known. 

Interferon AMa-n3. Interferon alfa-n3 is a glycoprotein produced from cultures of human leucocytes treated with Sendai virus. It is purifled initially by chromatography using a mou.se monoclonal antibody that binds to multiple species of human interferon. Subsequent purification involves incubation at 4°C and pH 2 to kill viruses and gel nitration chromatography. It then has a specific activity of about 2 x 108 lU. The drug is supplied in l-mL vials containing I mL of phosphate buffered saline solution, phenol as a preservative. and I mg of human serum albumin as a stabilizer. This solution should be kept at 2 to 8°C. Therapeutic indications and side effects of interferon alfa-n3 are. similar to those described for interferons alfa-2a and alfa-2b. 

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