Human serum albumin-drug interactions

Hanai, T., Miyazaki, R., and Kinoshita, T., Quantitative analysis of human serum albumin-drug interactions using reversed phase and ion-exchange liquid chromatography, Anal. Chim. Acta, 378, 77, 1999. 

Table 18 Human serum albumin-drug binding affinity and drug properties. rrSTi represents log k measured using an immobilized-HSA phase. nKa represents predicted log hsa-represents log k of acidic compounds at pH 7.4. k represents log k of basic compounds at pH 7.4. MIFa and MIFb represents the molecular interaction energy values of acidic and basic compounds, resepectively. nKs represents log nST measured using a modified Hummel-Dreyer method. nJQ, nKs, nSTg and nKj represent values. PB and PB2 represent the binding %. Log Pc are predicted log P values, and log Pm are measured values. 7.4 represents pH 7.4. Reproduced by permission of Bentham Science, ref. 20.

The ability of proteins to form enantioselective interactions with a large variety of drugs is used in chiral affinity chromatography. Protein CSPs that are most frequently used for the enantioseparation of pharmaceuticals include bovine serum albumin (BSA), human serum albumin... 

Benkestock, K., Edlund, P. O., Roeraade, J. Electrospray ionization mass spectrometry as a tool for determination of drug binding sites to human serum albumin by noncovalent interaction. Rapid Commun Mass Spectrom 2005, 19, 1637-1643. 

Erostell-Karlsson, A., Remaeus, A., Roos, H., Andersson, K, Borg, P., Hiimalainen, M. and Karlsson, R. (2000) Biosensor analysis of the interaction between immobilized human serum albumin and drug compounds for prediction of human serum albumin binding levels. Journal of Medicinal Chemistry, 43, 1986-1992. 

Desfosses et al. [328] measured binding of oxyphenyl betazone to the N-ter-minal peptic fragment of human serum albumin (HSA) in aqueous buffer and AOT/isooctane-RMs. The peptide affinity for the drug did not decrease in RMs. The interactions of HSA at membrane mimetic interface and its subsequent unfolding was suggested to constitute a drug release facilitating mechanism. 

Chiral separations on protein-based phases may also provide useful information on drug interactions. For instance, the effect of the individual enantiomers of warfarin on the enantioselectivity of human serum albumin toward benzodiazepinones has been studied using a human serum albumin... 

QSRR analysis of HPLC data determined on an immobilized human serum albumin (HSA) column helped to propose the topography of two binding sites of different affinity to benzodiazepine enantiomers 1143.163). Also, the mechanism of interaction of phenothiazine neuroleptics with melanin was rationalized by means of QSRR analysis of HPLC retention data [132,164]. Another QSRR study concerned the interactions of drugs with immobilized keratin and collagen [ 165). 

N. A. Brown, E. Janchen, W. E. Muller, and U. WoUert, Optical studies on the mechanism of the interaction of the enantiomers of the anticoagulant drugs phenprocoumon and warfarin with human serum albumin. Mol. Pharmacol, 13 70 (1977). 

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. 

Protein interactions have been investigated by ITP (D6). It has, for example, been possible to determine the number of sodium dodecyl sulfate (SDS) molecules bound to bovine serum albumin (H14, H15) and to investigate the binding of drugs such as indomethacin to human serum albumin (H15). This method could be of value in pharmacokinetic studies. 

Table 7.7 Molecular properties of some acidic compounds, logn represents the Human Serum Albumin (HSA)-drug binding affinity, from ref. 13. lognSf represents the HSA-drug binding affinity measured using a two-column system, from ref. 13. pKl are reference values, from ref. 13 TpKl values were measured by ion-exchange liquid chromatography. Mlm represents the molecular interaction eneigy calculated for the molecular-form compound, and Mlj the molecular interaction energy calculated for the ionic-form compound (kcal moP ).

D. S. Hage, T. A. G. Noctor and I. W. Wainer, Characterization of the protein binding of chiral drugs by high-performance affinity chromatography, interaction of R- and 5-ibuprofen with human serum albumin,/. Chromatogr., A, 1995, 693, 23-32. 

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