Sakai T, Awata N, Watanabe J
Pharmaceuticals Research Center, Kanebo, Ltd., Osaka, Japan.
Chem Pharm Bull (Tokyo). 1990 May;38(5):1349-52. doi: 10.1248/cpb.38.1349.
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.
以抗组胺药富马酸依美斯汀（KG-2413）为研究对象，通过关注其流入、流出及代谢过程，对大鼠和豚鼠肝脏转运的种间差异进行了研究。快速门静脉注射时，当依美斯汀注射浓度在2 microM至10 mM之间变化时，大鼠在注射后18秒、豚鼠在注射后25秒时，肝脏对总放射性化合物的摄取率超过给药剂量的90%。这表明依美斯汀流入肝脏的速度极快，且在流入过程中不存在种间差异。快速门静脉注射100 microM溶液后，大鼠肝脏中未变化的依美斯汀的消失情况呈双指数曲线，而豚鼠则呈单指数曲线。这种差异可能与依美斯汀与肝脏组织结合的种间差异有关。使用房室模型分析了肝脏中总放射性化合物和未变化的依美斯汀消失的时间过程，以考察流出和代谢过程。结果发现，依美斯汀的代谢速率常数存在明显的种间差异，但其流出速率常数不存在明显的种间差异。
