caa a22 4500 477128467 CHVBK 20180405111656.0 cr unu---uuuuu 170330e19971101xx s 000 0 eng 10.1023/A:1012138604016 doi (NATIONALLICENCE)springer-10.1023/A:1012138604016 Species Differences of Serum Albumins: I. Drug Binding Sites [Elektronische Daten] [Takamitsu Kosa, Toru Maruyama, Masaki Otagiri] Purpose. The purpose of this study was the classification and identification of drug binding sites on albumins from several species in order to understand species differences of both drug binding properties and drug interaction on protein binding. Methods. Binding properties and types of drug-drug interaction on the different albumins were examined using typical site I binding drugs, warfarin (WF) and phenylbutazone (PBZ), and site II binding drugs, ibuprofen (IP) and diazepam (DZ) on human albumin. Equilibrium dialysis was carried out for two drugs and the free concentrations of drugs were then treated using the methods of Kragh-Hansen (Mol. Pharmacol. 34. 160−171, (1988)). Results. Binding affinities of site I drugs to bovine, rabbit and rat albumins were reasonably similar to human albumin. However, interestingly, those to dog albumin were considerably smaller than human albumin. On the other hand, binding parameters of DZ to bovine, rabbit and rat albumins were apparently different from those of human albumin. These differences are best explained by microenvironmental changes in the binding sites resulting from change of size and/or hydrophobicity of the binding pocket, rather than a variation in amino acid residues. Conclusions. We will propose herein that mammalian serum albumins used in this study contain specific drug binding sites: Rabbit and rat albumins contain a drug binding site, corresponding to site I on human albumin, and dog albumin contains a specific drug binding site corresponding to site II on the human albumin molecule. Plenum Publishing Corporation, 1997 drug binding site nationallicence human serum albumin nationallicence experimental animal serum albumins nationallicence species difference nationallicence Kosa Takamitsu Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kumamoto, Japan aut Maruyama Toru Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kumamoto, Japan aut Otagiri Masaki Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kumamoto, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1607-1612 0724-8741 14:11<1607 1997 14 11095 https://doi.org/10.1023/A:1012138604016 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012138604016 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kosa Takamitsu Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kumamoto, Japan aut NATIONALLICENCE 700 1- Maruyama Toru Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kumamoto, Japan aut NATIONALLICENCE 700 1- Otagiri Masaki Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kumamoto, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1607-1612 0724-8741 14:11<1607 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence SWISSBIB 477128467 BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer