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机构地区:[1]华北制药集团新药研究开发有限责任公司,河北石家庄050011 [2]广州中医药大学临床药理研究所,广东广州510405
出 处:《中国中药杂志》2010年第13期1750-1753,共4页China Journal of Chinese Materia Medica
基 金:国家自然科学基金项目(30672637)
摘 要:目的:研究不同毒性剂量雄黄在大鼠体内的动力学行为及组织中的总砷分布。方法:SD大鼠分别单次灌服3.738,1.869,0.935 g.kg-1雄黄,测定不同剂量组大鼠药后0~96 h内的血砷、尿砷浓度,以及药后96 h各主要脏器的总砷含量。结果:大鼠单次灌服不同剂量雄黄,高剂量组总砷在大鼠体内的分布半衰期和消除半衰期分别为7.73,17.21 h,均短于中剂量组和低剂量组。高、中、低剂量组的表观分布容积分别为10.8,5.6,3.9 L.kg-1;总清除率分别为0.437,0.16,0.111 L.h-1.kg-1;药后0~96 h内尿总砷的排泄量占雄黄给药量的5.5%~13.0%;药后96 h各主要脏器、组织中均可检测到砷,以肾上腺、膀胱、卵巢中分布较多,肝、脾、肺、肾次之,心、大脑、胃、睾丸中分布较少。结论:在毒性剂量下,雄黄的动力学参数随剂量大小而改变,表明其在大鼠体内存在非线性动力学过程。Objective: To study the toxicokinetics and tissue distribution of total arsenic after giving different doses realgar to rats.Method: The concentration of arsenic in blood,urine and main organs were determined after single oral administration of 3.738,1.869,0.935 g·kg-1 realgar in rats.Result: The distribution half life(t1/2α) and elimination half life(t1/2β) of total arsenic were 7.73 h and 17.21 h respectively in high dose group.The apparent distribution volume(Vd) were 10.8,5.6,3.9 L·kg-1 respectively,the total clearance(Cltot) were 0.437,0.16,0.111 L·h-1·kg-1 respectively in the three groups.The excretion of total urine arsenic got rid of 5.5%-13.0% of realgar which given to rats in 96 hours.Arsenic could be detected distributing into rat′s main organs and tissues after administration of a single dose.Suprarenal gland,bladder and ovary accumulated most of the arsenic,while liver,spleen,lung and kidney accumulated less.Heart,brain,stomach and testis accumulated the least amount.Conclusion: It has non-linear dynamics in the body of rats in toxic doses as the kinetics of realgar was changed according to the dosage.
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