Hepatic transport of an antiallergic agent, emedastine difumarate: interspecies difference in rats and guinea pigs.
Interspecies differences in the hepatic transport of an antiallergic agent, emedastine difumarate (KG-2413), were investigated in rats and guinea pigs, taking notice of the influx, efflux and metabolic processes. When the concentration of emedastine in the injection was varied from 2 microM to 10 mM, the extraction ratio of total radioactive compound to the liver at 18 s in rats and 25 s in guinea pigs after the rapid portal injection was more than 90% of the dose. This suggested that the influx velocity of emedastine into the liver was extremely fast, and that there was no interspecies difference in the influx process. The disappearance of unchanged emedastine from the liver was described by biexponential curve in rats and monoexponential curve in guinea pigs after rapid portal injection of 100 microM solution. This difference might be related to the interspecies difference in the binding of emedastine to the liver tissue. The time courses of disappearance of total radioactive compound and unchanged emedastine from the liver were analyzed using a compartment model for the examination of the efflux and metabolic processes. Emedastine was observed to have a pronounced interspecies difference in metabolic rate constant, but there was no pronounced interspecies difference in its efflux rate constant.
Sakai
T
T
Pharmaceuticals Research Center, Kanebo, Ltd., Osaka, Japan.
Awata
N
N
Watanabe
J
J
D000818:Animals; D001562:Benzimidazoles / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D001562:Benzimidazoles; C043345:emedastine