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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 dynamic behavior of realgar with different toxic doses in rats and the distribution of total arsenic in tissues. Methods: SD rats were given a single dose of Realgar at 3.738, 1.869 and 0.935 g.kg-1 respectively for determination of arsenic and arsenic concentrations within 0-96 h after drug exposure in rats. Total arsenic content of organs. Results: The half-life and elimination half-life of total arsenic in rats fed with different doses of realgar at high and low doses were 7.73 and 17.21 h, respectively, which were both shorter than those of middle-dose and low-dose groups. The apparent volume of distribution of high, medium and low dose groups were 10.8,5.6,3.9 L.kg-1 respectively; the total clearance rate was 0.437,0.16,0.111 Lh-1.kg-1; within 0-96 h after treatment Total urinary excretion of total arsenic accounted for 5.5% ~ 13.0% of the dose of realgar. Arsenic was detected in all major organs and tissues at 96 hours after drug administration, with more distribution in the adrenal gland, bladder and ovary, Lung, kidney followed, heart, brain, stomach, testis distribution is less. Conclusions: At toxic doses, the kinetic parameters of realgar change with the dose, indicating that there is a nonlinear kinetic process in the rat.