摘要
目的初步探讨四硫化四砷(As4S4)的动物药动学规律。方法原子分光光度法测定As4S4小鼠单次灌胃后血砷浓度以及组织、排泄物中总砷含量。以3P97软件进行药动学参数估算。结果小鼠单次灌胃As4S4的药-时变化符合一房室模型,吸收不完全,消除较慢,其消除半衰期9~12 h。口服给药后砷在小鼠体内分布广泛,主要分布在体脂、毛、皮、肝、肾、脾和子宫。砷主要从粪、尿排泄。结论小鼠灌胃As4S4血中和组织中能达到一定浓度,但是吸收有限,因而相对较为安全。消除半衰期较长,值得注意。
Abstract
OBJECTIVE To investigate the pharmacokinetic behavior after an intragastric(ig) administration of a single dose of tetra-arsenic tetra-sulfide(As4S4) in mice.METHODS Atomic absorption spectrometry was used to determine the total concentration of arsenic in bio samples,including blood,tissue and excreta.RESULTS The concentrationtime curves of As4S4 in blood after an ig of 3 different dosages in mice were discribed by an one-compartment model with the 1st order absorption calculated by the program 3P97.The absorption of As4S4 was insufficient.It was eliminated slowly,with the half-life of about 9~12 h.Arsenic was widely distributed in many tissues,mainly in body fat,hair,skin,liver,kidney,spleen and uterus.It was mainly excreted in feces and urine.CONCLUSION Arsenic is detected in the blood and many tissues of mice after a single dose of As4S4.However,its absorption is insufficient,so that it is relative safe for ig administration.It is important that t1/2(Ke) is long.
关键词
四硫化四砷 /
药动学 /
原子吸收分光光度法
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Key words
tetra-arsenic tetra-sulfide /
pharmacokinetics /
atomic absorption spectrometry
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温磊;楼雅卿;江滨;陆道培.
四硫化四砷动物药动学研究[J]. 中国药学杂志, 2006, 41(08): 619-622
WEN Lei;LOU Y-qing;JING in;LU Do-pei.
Pharmacokinetics of Tetra-Arsenic Tetra-Sulfide in Mice [J]. Chinese Pharmaceutical Journal, 2006, 41(08): 619-622
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参考文献
[1]HAO H Y,TENG Z P,LU D P. Apoptotic effect of tetra-arsenic tetra-sulfide on acute promyelocytic leukemia cell line NB4[J].Chin J Pharmacol Toxicol(中国药理与毒理学杂志),2002,16(1): 37-40.
[2] LIU Y F,JIANG B,LU D P. Arsenic sulfide induces NB4 apoptosis and arrests cell growth in G2/M phase[J].Chin J Hematol(中华血液学杂志),2000,21:647-648.
[3]LU D P,QIU J Y,JIANG B,et al. Effective treatment of acute promyelocytic leukemia (APL) with tetra-arsenic tetra-sulfide (As4S4),a monoinstitutional study (abstract)[J] .Blood,1999,94:698a.
[4]LU D P,WANG Q. Current study of APL treatment in China[J].Int J Hematol,2002(Suppl 1):316-318.
[5]LU D P,QIU J Y,JIANG B,et al. Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot repor[J].Blood,2002,99:3136-3143.
[6]QIN X Y,LI G X,JIANG B,et al.Determination of arsenic in blood,urine and hair of acute promyelocytic leukemia (APL) patients after taking arsenic sulfides[J] .Stud Trace Elements Health(微量元素与健康研究),18(68): 15-17.
[7]HUNDER G,JAVDANI J,ELSENHANS B,et al.Use of γ-spectrometry for simultaneous determination of 210Pb,73As,109Cd,203Hg and 59Fe distribution and excretion in rats at low doses[J].Toxicology,2000,150(1-3): 69-82.
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脚注
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