雄黄单次和多次给药在大鼠体内的药物动力学和组织分布  

Pharmacokinetics Study of Realgar and Its Tissue Distribution in Rats after Single Dose and Multiple Dose of Oral Administration

作　　者：汤毅珊[1] 欧卫平[1] 王宁生[1] 刘启德[1] 

机构地区：[1]广州中医药大学临床药理研究所,广州510405

出　　处：《中药新药与临床药理》2008年第5期372-376,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金资助项目(30672637)。

摘　　要：目的研究雄黄中的砷在大鼠体内的药物动力学和组织分布。方法大鼠单次、多次灌服雄黄,采用微波消解-原子荧光光度法测定药后一系列时间点的血砷浓度和脏器、组织中的砷含量。应用PK Solutions 2.0^(TM)药动学软件计算药动学参数。结果雄黄(75 mg·kg^(-1))灌胃给药后,雄黄中的砷只有少量吸收进入血液中,吸收、分布和消除半衰期分别为4.30,12.59,22.70 h;血砷浓度在药后3 h和12 h分别达到峰浓度(46.0,42.0μg·L^(-1)。雄黄(75mg·kg^(-1)·d^(-1))连续灌胃给药15 d,从第7天起达到稳态浓度,停药后2周的血清中未检出砷,消除半衰期为43.61 h。单次给药后,在大鼠各主要脏器、组织中均可检测到砷,以脾、毛发、肺和肾上腺中分布较多,肾、心、肝、膀胱、皮肤次之;大脑、睾丸、肌肉、胫骨中分布较少,多次给药后砷除了同样在肾上腺、肺、毛发和脾分布较多外,在肾和膀胱的积累显著增加。停药2周后,砷在各脏器组织(心除外)中的含量普遍显著降低,降幅从21.1%到69.5%不等。结论雄黄中的砷只有少量可溶性砷吸收进入血液中,单次灌胃给药后,雄黄中的砷在大鼠体内吸收、分布和消除均较缓慢。多次灌胃给药延缓了砷在体内的消除。雄黄中的砷在大鼠体内分布广泛;首次发现砷在肾上腺中有较高的蓄积,提示肾上腺可能是雄黄作用的靶器官之一。Objective To study the pharmacokinetics of arsenic from Realgar in rats and tissue distribution after single dose and multiple dose of oral administration. Methods Rats were orally administrated with single dose（75 mg· kg-1） and multiple dose （75 mg· kg-1· d-1, one dose per day, 15 continuous days） of Realgar respectively. Arsenic concen- trations in serum and arsenic contents in organs and tissues were determined by atomic spectrophotofluorimetry after mi- crowave digestion pretreatment. PK Solutions 2.0^TM software was used to process experimental data. Results Half - life of absorption, distribution and elimination of arsenic in rat serum were 4. 30, 12.59 and 22.70 hours respectively after single dose administration. Arsenic concentration reached to maximum concentration （46.0 μg· L^-1） at 3 hours after administration, and then decreased. Twelve hours after administration arsenic concentration increased to the second peak concentration （42.0 μg· L^-1）. When Realgar was orally administrated in a fixed dose and at a fixed interval, arsenic concentration maintained a steady state from the 7th day after the first administration, and the half- life of elimination was 43.61 h. Arsenic could be detected in the main organs and tissues of rats after administration of a single dose. The ar- senic was most accumulated in the spleen, hair, lung and suprarenal gland organs, and kidney, heart, liver, bladder and skin came next. Brain, testis, muscle and tibia had the least amount of arsenic. After 15 continuous clays of admin- istration, arsenic contents in kidney and bladder tissues increased appreciably besides suprarenal gland, lung, hair and spleen. After 2 weeks of discontinuation, arsenic contents in organs and tissues decreased by 21.1% - 69.5 % except for heart. Conclusion Small amount of soluble arsenic in Realgar was absorbed in blood circulation. Absorption, distribution and elimination of arsenic from Realgar proceed slowly in rats after single dose of oral administration. Multiple dose o

关 键 词：雄黄 砷 药物动力学 组织分布 微波消解-原子荧光光度法 大鼠 

分 类 号：R285.5[医药卫生—中药学]