Effect of Temperature on Binding of Warfarin by Human Serum Albumin

Human Serum Albumin Binding of Novel Antiretroviral Nucleoside Derivatives of AZT

“…By analyzing the effect of the fatty acids on the bound fraction of AZT, it was observed that the fatty acid molecules produced a conformational change in the cavity of site I, leading to AZT increased affinity for HSA (Table 2), as it was previously observed for warfarin (24,25). In addition, inspection of Table 3 showed that a temperature variation produced a similar effect on AZT binding to that reported for warfarin (22). From the results of Table 4, it is possible to deduce that the bound fraction, and in consequence the binding affinity, of compounds 2-7 were increased in different proportions if compared with AZT.…”

“…This fact indicated that an entropy controlled process for binding of AZT to the HSA molecule took place, with a poor significance of the enthalpy changes in the overall binding process. This characteristic was previously described for warfarin, a high specific HSA site I drug (22,23), indicating that the entropy-driven binding process may be a characteristic for site I drugs. The slight effect of temperature in the bound fraction was of relevant importance for this study, because it allowed us to work at lower than physiological temperatures.…”

“…It was found that warfarin and salicylate act as specific site I markers (6,22). Since the primary binding site for warfarin and salicylate are near identical, in the present study salicylate was used in order to avoid toxicity risks derived from the use of the potent anticoagulant warfarin (22), while diazepam was used as a site II marker (6). According to the results obtained, it could be seen that AZT was displaced from its binding site by salicylate, indicating that it was bound to site I, while diazepam produced a considerable increase in AZT bound fraction.…”

Effect of bile acids on the binding of drugs and dyes to human albumin

“…The values of n and k found in this study for HABA, sulphadimethoxine and warfarin are similar to those quoted in the literature (Oester et al 1976;Vallner 1977;Bowmer & Lindup 1980); but for methyl orange, k, and k2 are an order of magnitude greater than those reported by Bowmer & Lindup (1980). This discrepancy may be due to differences in buffer composition because chloride ions were present in the phosphate buffer used by Bowmer & Lindup (1980) and these have been reported to reduce the methyl orange-HA interaction (Klotz & Urquhart 1949).…”

Determination of unbound drug concentration and protein-drug binding fraction in plasma

“…The major limitation of this method is that a large volume of sample is needed to observe a clear g-plateau. For example, it was reported that 45 mL of salicylate-human serum albumin (HSA) mixed solution (Keresztes-Nagy et al, 1972) and 60 mL of warfarin-HSA mixed solution (Oester et al, 1976) were used to obtain clear g-plateaus using a Sephadex G-25 column (25 cm  1 mm i.d.). Sebille et al (1978) employed this method with a high-performance liquid chromatography (HPLC) system using a 5-10 mm Bondagel column (30 cm  3.9 mm i.d.)…”