| 초록 |
The purpose of the present study was to examine the pharmacokinetic characteristics of arsenic hexaoxide( $As_4O_6$ ), a novel anticancer compound, after i.v. bolus and oral administration in rats. We developed an ICP-Mass based method to analyze arsenic hexaoxide levels in plasma, bile, urine, feces, and tissue and validated the method. Arsenic hexaoxide rapidly disappeared from the plasma by 10 min( $ alpha$ phase) after i.v. administration, which was followed by the late disappearance in the $ beta$ phase. The mean plasma half-lives( $t_{1/2}$ ) of arsenic hexaoxide at the a and $ beta$ phase when administered at a dose of 5 mg/kg were 1.57 and 29.8 min, respectively. The maximum plasma concentration( $C_{max}$ ) was 230 ng/mL, after oral administration of arsenic hexaoxide at a dose of 50 mg/kg. The bioavailability, which was calculated from the dose-adjusted ratio, of the oral administered arsenic hexaoxide was 1.61%. Of the various tissues tested, arsenic hexaoxide was mainly distributed in the spleen, lung, liver and kidney after oral administration. Arsenic hexaoxide levels in the spleen or lung at 24 hr after oral administration were higher than those of maximum plasma concentration( $C_{max}$ ). The cumulative amounts of arsenic hexaoxide found in the urine by 48 hr after the administration of 50 mg/kg were 5-fold higher than those in the bile. However, the cumulative amounts in the feces were 10-fold higher compared with those of urine, suggesting that arsenic hexaoxide is mostly excreted in the feces. In conclusion, our observations indicated that arsenic hexaoxide was poorly absorbed from the gastro-intestinal tract to the blood circulation and transferred to tissues such as the spleen and lung at 24 hr after oral administration. Moreover, the majority of arsenic hexaoxide appears to be excreted in the feces by 48 hr after oral administration. |
