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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。
A single gavage method was used to study the absorption, distribution and excretion of p-phenylphthalamic acid (PPA) in rats by high performance liquid chromatography (HPLC) Time-varying process and toxicokinetic parameters. The results showed that the absorption rate of phenylpenic acid in the digestive tract was fast, the half-absorption period was only (0.15 ± 0.11) h and the peak plasma concentration (t max) was (0.68 ± 0.37) h, and peak plasma concentration (C max) was (141.48 ± 27.87) mg / L. Phenylalanine was distributed rapidly and distributed widely in rats, and the half-distribution period (t 1/2 ) Was 0.22 ± 0.18 h, and the apparent volume of distribution (Vz / F) was (17.54 ± 7.71) L / kg. Phenylalanine was rapidly eliminated from rats and its clearance rate (1.32 ± 0.51) (L / h) / kg, mean residence time in vivo (MRT_ (0 -∞)) was (25.69 ± 2.93) ± 1.44) h, more than 95% of Phetidine can be eliminated from rats after about 35 h. The results showed that the concentration-time curve of pheneline presented a bimodal phenomenon, suggesting that there may be intestinal-hepatic circulation in rats. From the rat intragastric administration within 24 h, the detected organizations and organs can be detected in the penehyclidine, its concentration from high to low were: kidney> lung> liver> heart> spleen> muscle > Testis> fat> brain, kidney drug content of 192.7μg / g, while only the targeted distribution coefficient (t_e) value of the kidney tissue is greater than 1 (4.77), suggesting that pephenylline in the rat body distribution of the kidney has Relatively high selectivity. The results of the excrement research showed that the total amount of phenytoin excreted with the feces was only 1.45% of the dose, and no peptidyl acid was detected in the urine.