사염화탄소와 갈락토사민 간장해 시의 오큐빈의 체내동태 차이 = Different Pharmacokinetics of Aucubin in Rats of Carbon tetrachloride and D-Galactosamine-induced Hepatic Failure

다국어 초록 (Multilingual Abstract)

Pharmacokinetics of aucubin, an irdoid glucoside, was compared in rats of experimental hepatic failure(EHF). EHF was induced by CCl4 or D-galactosamine pretreatment. This work was designed to find out any differences in the pharmacokinetics of aucubin that may explain the different protective effect of aucubin on CCl4- and galactosamine-induced EHF : aucubin reportedly protected CCl4-inducing hepatotoxicity effectively, but did not for galactosamine-hepatotoxicity. EHF was induced by intraperitoneal injection of CCl4(0.9Ml/kg) or galactosamine(250mg/kg) to Wistar rats 24 hr before the pharmacokinetic study. The rats were fasted during the 24 hr. Aucubin was iv injected at a dose of 15mg/kg and the plasma aucubin was assayed by HPLC. There were no significant differences in the pathophysiologies(body weight, liver weight, GTP, hematocrit, blood cell distribution and plasma protein binding of aucubin) between the two EHF models except GOP which was significantly (p<0.05) higher in CCl4-than in galactosamine-EHF. On the other hand, pharmacokinetics of aucubin such as total clearance(CLt), distribution volume at steady-state(Vdss), and mean residence time(MRT) differed significantly(p<0.05) between the models : for example, CLt was increased two fold by CCl4, but not by galaclosamine ; Vdss in galactosamine-EHF was higher than that in CCl4-EHF ; MRT was decreased by CCl4, but increased conversely by galactosamine. The increase of CLt(and decrease of MRT) in rats of CCl4-EHF was contrary to the general expectation for the hepatic failure : most of the hepatic failures have been known to decrease CLt of the administered drugs. Whether the difference in the pharmacokinetics is responsible for the different protective effect of aucubin against the two EHF models is of interest. However, much more studies on biliary excretion, urinary excretion, and hepatic uptake in cellular level should be preceded before any conclusions are made on the role of different pharmacokinetics on the different pharmacology of aucubin.