血清アルブミン上のジアゼパム結合サイトにおける薬物相互作用の解析法 ＥＬＩＳＡによるグリチルレチン酸測定法を応用したスクリーニング法

Abstract

In order to clarify the binding site of drugs on human serum albumin (HSA), competition studies were carried out using ELISA for glycyrrhetic acid (GA), which is mainly bound to the diazepam site on HSA.The release of GA from HSA was detected as a displacement by the various drugs [bezafibrate (B), delapril HCI, diclofenac Na (D), doxifluridine, famotidine, ibuprofen (I), loxoprofen Na (L-1) and its metabolite (loxoprofen Na trans-OH (L-2)), pravastatin Na]. The percentages of GA release by the addition of I, D, L-1, L-2, which belong to nonsteroidal anti-inflammatory drugs, and B were 96.0%, 86.5%, 25.4%, 25.6% and 12.6% respectively. In addition, the percentages of GA release by addition of the other 4 drugs ranged between 3. 2 and 4.1%. These results showed that I and D were strongly bound to the diazepam site, while the binding of L-1, L-2 and B was weak. Thus, L-1, L-2 and B may predominantly bind to other site (s) on HSA.Therefore, ELISA for GA was suggested to be helpful for studying the binding site (diazepam binding site) of the drugs on HSA.