Binding of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1, 4-diazepin-1-yl) benzimidazole difumarate (KG-2413) to serum or plasma proteins in man, guinea pig and rat.
Human, guinea pig and rat sera or plasma protein binding of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1, 4-diazepin-1-yl)benzimidazole difumarate (KG-2413) were investigated by equilibrium dialysis. There were pronounced interspecies differences in binding affinity and binding capacity which were the highest in guinea pig and human species, respectively. In humans, the binding index (n1P1/Kd1) of isolated alpha 1-acid glycoprotein (alpha 1-AG) was seven times higher than that of isolated albumin, and the dissociation constant for human serum at the high affinity binding site was comparable to that for alpha 1-AG. These facts suggested that the free base of KG-2413 was mainly bound to alpha 1-AG in human serum. The contribution of albumin to the binding of KG-2413 in guinea pig and rat plasma may be relatively small. The interspecies differences in KG-2413 binding observed in this study may be due to species differences in the binding affinity and/or capacity of alpha 1-AG.
Sakai
T
T
Pharmaceuticals Research Center, Kanebo, Ltd., Osaka, Japan.
Hamada
T
T
Awata
N
N
Watanabe
J
J
D000293:Adolescent; D000328:Adult; D000818:Animals; D001562:Benzimidazoles / Q000097:blood*; D003956:Dialysis; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D009961:Orosomucoid / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism
D001562:Benzimidazoles; D009961:Orosomucoid; D012709:Serum Albumin; C043345:emedastine