Species Differences in the Binding of Phenylbutazone to Plasma Albumin

Abstract

The binding of phenylbutazone to plasma albumins from man, rat, rabbit and dog has been measured at 37°C by equilibrium dialysis. Species differences were found both in the number of phenylbutazone binding sites per albumin molecule and the affinity of such sites for the drug. Using the binding parameters from this study we have shown how it is possible to estimate the effect of plasma albumin binding on the distribution of a drug in the body. These calculations suggest that although phenylbutazone has a stronger affinity for human plasma albumin than for plasma albumins from the other 3 species it is unlikely that the longer biologic half life of the drug in man can be attributed solely to a difference in plasma binding. Using the binding parameters for human plasma albumin the effect of complete displacement of phenylbutazone from plasma and tissue binding sites on the concentration of free drug in plasma has also been estimated.

Lysine residue 199 of human serum albumin is modified by acetylsalicylic acid

“…Thus, the binding of acetriozate [1,2,4] and phenylbutazo'ne [11 ] is enhanced and concomitantly with the latter observation flufenamic acid binding is decreased.…”

Predicting Passive and Active Tissue:Plasma Partition Coefficients: Interindividual and Interspecies Variability

“…A number of published articles have discussed interspecies variations in the tissue distribution of organic chemicals . These variations have been shown to depend upon a number of factors, including differences in tissue composition, plasma protein binding, tissue DNA concentrations, and active transporter specificities and affinities . These studies support the need for the use of species‐specific K t:pl values for PBPK modeling and risk assessment applications.…”

The Investigation of the Binding of 6-Mercaptopurine to Site I on Human Serum Albumin

“…Detailed warfarin and phenylbutazone binding studies by the use fluorescence, absorption spectrometry and near-UV circular dichroism showed that the both of the ligands bind with high-affinity to a region in subdomain IIA [ 5 , 22 , 35 , 54 , 55 ]. The X-ray crystalographic analysis of warfarin–HSA and phenylbutazone–HSA complexes provided the more information about the interactions between those drugs and HSA in binding site.…”