Abstract
The inhibition parameters of various drugs (inhibitor, I) for the reaction of p-nitrophenyl acetate (substrate, S) with human serum albumin (HSA) could not be directly determined, because HSA has two esterase-like active sites for S (i.e. R and T sites) and three drug binding sites (i.e. R, T and U sites) [Ozeki et al., Chem. Pharm. Bull., 28, 525 (1980)]. In the present study, the dissociation constants between I and the individual binding sites on HSA, KI, R, KI, T and KI, U, were determined by analog computer simulation of the inhibition. Clofibric acid, ibuprofen and dansylsarcosine were found to bind solely to the R site, and their KI, R values were determined. Flufenamic acid, ethacrynic acid and salicylic acid bind primarily to the R site and then to the T site, and their KI, R and KI, T values were estimated. The KI, U and KI, R values for phenylbutazone and sulfinpyrazone were also determined, and their KI, U values were smaller than their KI, R values. It is likely that warfarin binds primarily to two binding sites unconcerned with the esterase-like activities and then to the R site of HSA, and these three dissociation constants were estimated. Since this kinetic method distinguishes the drug binding sites on HSA and gives the dissociation constants for the individual sites, it is very useful for studies on drug interaction with HSA.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.