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SB-31의 Glycyrrhizin을 지표로 한 Rat과 Rabbit에서의 약물동태 및 심혈관계에 대한 연구
강원구,박용순,이동흠,권광일 충남대학교 약학대학 의약품개발연구소 1999 藥學論文集 Vol.15 No.-
SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rat's and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingredient for the pharmacokinetics of SB-31. The rat`s blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were 98.06±6.07ml, 0.33±0.05hr^-1 and 65.46±11.19ml, 0.68±0.25hr^-1, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were 235.24±30.72ml, 0.13±0.36 hr-1 and 341.32±28.58ml, 0.27±0.04 hr^-1, respectively. "WinNonlin" was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pharmacokinetic model. The data were best described by using a weighting factor of 1/y-2. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (-dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about 6.9~11.5%. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.