苯肽胺酸在大鼠体内的毒物动力学及组织分布  

Toxicokinetics and tissue distribution of N-phenyl-phthalamic acid in male rats

作　　者：韦思华[1] 代玲玲[1] 周峰[1] 李龙[1] 

机构地区：[1]华中科技大学同济医学院公共卫生学院卫生毒理学系教育部环境与健康重点实验室,武汉430030

出　　处：《农药学学报》2016年第1期71-76,共6页Chinese Journal of Pesticide Science

摘　　要：采用单次灌胃染毒法,通过高效液相色谱仪测定,研究了苯肽胺酸(N-phenylphthalamic acid,PPA)在大鼠体内的吸收、组织分布及排泄情况,以及其血药浓度经时变化过程和毒物动力学参数。结果表明:苯肽胺酸经消化道吸收速率较快,其半吸收期t_(1/2ka)仅为(0.15±0.11)h,血药浓度的达峰时间(t_(max))为(0.68±0.37)h,血药峰浓度(C_(max))值为(141.48±27.87)mg/L;苯肽胺酸在大鼠体内分布快且分布范围广,半分布期(t_(1/2α))为(0.22±0.18)h,表观分布容积(Vz/F)为(17.54±7.71)L/kg;苯肽胺酸从大鼠体内消除较快,其清除率(CLz/F)为(1.32±0.51)(L/h)/kg,在体内平均驻留时间(MRT_(0-∞))为(25.69±2.93)h,消除半减期(t_(1/2z))为(7.77±1.44)h,约35 h后95%以上的苯肽胺酸可从大鼠体内消除。研究发现:苯肽胺酸的浓度-时间曲线呈现双峰现象,提示其在大鼠体内可能存在肠-肝循环。从大鼠灌胃染毒后至24 h内,被测各组织、脏器中均可检出苯肽胺酸,其浓度由高到低依次为:肾脏>肺>肝脏>心脏>脾脏>肌肉>睾丸>脂肪>大脑,肾脏中药物含量达192.7μg/g,同时仅肾脏组织的靶向分布系数(t_e)值大于1(4.77),提示苯肽胺酸在大鼠体内分布时对肾脏具有相对较高的选择性。排泄物研究结果显示,苯肽胺酸随粪便排出的总量仅占给药量的1.45%,而尿液中未检出苯肽胺酸。To explore the absorption,tissue distribution,excretion,the change of drug blood concentrations over time and the kinetic parameters of N-phenyl-phthalamic acid（PPA） in male rats,single dose gavage was applied in the experiments.And the PPA was determined by high performance liquid chromatography.The results show that the gastrointestinal absorption was fast.In serum,the half absorption phase t1/2ka was only（0.15 ± 0.11） h.The maximum concentration time point tmax was（0.68 ± 0.37） h,and the peak concentration（Cmax） was（141.48±27.87） mg/L.The tissue distribution in rat was fleetly and widely.The half distribution stage t1/2α was（0.22±0.18） h,and the apparent volume of distribution Vz/F was（17.54 ± 7.71） L/kg.The drug eliminate rapidly in vivo,and its clearance was CLz/F（1.32 ± 0.51）（L/h） /kg.The average residence time MRT0-∞ was（25.69 ± 2.93） h,and the elimination half life t1/2z was（7.77 ± 1.44） h.More than 95%of the PPA can eliminate from the body in35 h.In this study,the bimodal phenomena was observed in the concentration-time curve of PPA.The result suggested that the cause may be the enterohepatic circulation in rats.Within 24 h,PPA could be detected in the entire tissue samples after the oral administer.The concentration order from high to low was：kidneys,lungs,liver,heart,spleen,muscle,testis,fat,and the brain.Among those,the concentration of N-phenyl-phthalamic acid in kidney reached up to 192.7 μg/g,and the targeted distribution coefficient（te） was 4.77 which was higher than 1.00.It suggested that the distribution of PPA in vivo has a relatively high selectivity to the kidney.The result of excretion study revealed that the amount of PPA existed in the feces only account for 1.45%of the overall dosage,and no PPA was detected in urine.

关 键 词：苯肽胺酸 毒物动力学 大鼠 组织分布 高效液相色谱法 

分 类 号：S482.8[农业科学—农药学] S481.1[农业科学—植物保护]