caa a22 4500 47712755X CHVBK 20180405111654.0 cr unu---uuuuu 170330e19970401xx s 000 0 eng 10.1023/A:1012168020545 doi (NATIONALLICENCE)springer-10.1023/A:1012168020545 Interactions of Aldosterone Antagonist Diuretics with Human Serum Proteins [Elektronische Daten] [Norito Takamura, Toru Maruyama, Shamim Ahmed, Ayaka Suenaga, Masaki Otagiri] Purpose. The purpose of this study was to investigate the binding mechanism of aldosterone antagonist diuretics with human serum proteins, human serum albumin (HSA) and α1-acid glycoprotein (AGP), as well as to identify the binding sites of the drugs on these proteins. Methods. Binding activities of spironolactone (SP) and its pharmacologically active metabolite canrenone (CR) to serum and serum protein were examined by ultrafiltration and spectroscopic techniques. The data for the binding of these drugs to HSA were analyzed on the basis of a theoretical model of simultaneous binding of the ligands. Results. The binding percentages of antagonist diuretics SP and CR to human serum proteins were 88.0% and 99.2%, respectively, at therapeutic concentrations. SP bound strongly and almost equally to both HSA and AGP, but CR bound strongly only to HSA. In addition, the displacement results found using fluorescent probes and ultrafiltration methods demonstrated that SP bound to site I, particularly to the warfarin region on HSA, and to the basic binding site on AGP, while CR bound to the warfarin region on HSA. Conclusions. The limited results presented here stress the need for caution on coadministration of acidic drugs which bind to the warfarin region on HSA and basic drugs which bind to AGP with SP and its metabolite CR. Plenum Publishing Corporation, 1997 spironolactone nationallicence canrenone nationallicence drug interaction nationallicence human serum albumin nationallicence α1-acid glycoprotein nationallicence Takamura Norito Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kymamoto, Japan. aut Maruyama Toru Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kymamoto, Japan. aut Ahmed Shamim Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kymamoto, Japan. aut Suenaga Ayaka Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kymamoto, Japan. aut Otagiri Masaki Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kymamoto, Japan. aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 522-526 0724-8741 14:4<522 1997 14 11095 https://doi.org/10.1023/A:1012168020545 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012168020545 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takamura Norito Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kymamoto, Japan aut NATIONALLICENCE 700 1- Maruyama Toru Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kymamoto, Japan aut NATIONALLICENCE 700 1- Ahmed Shamim Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kymamoto, Japan aut NATIONALLICENCE 700 1- Suenaga Ayaka Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kymamoto, Japan aut NATIONALLICENCE 700 1- Otagiri Masaki Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862, Kymamoto, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 522-526 0724-8741 14:4<522 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer