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氯解磷定在急性辛硫磷中毒大鼠体内药代动力学 被引量:5

Pharmacokinetics of pralidoxime chloride in acute phoxim-poisoning rats
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摘要 目的 探讨氯解磷定 (PAM Cl)在急性辛硫磷中毒大鼠体内药代动力学性质变化和PAM Cl对乙酰胆碱酯酶 (AChE)的复能作用 ,为治疗辛硫磷中毒合理利用PAM Cl提供科学依据。方法 给大鼠腹腔注射 80mg kgPAM Cl,采用高效液相色谱法测定PAM Cl血浆浓度。PAM Cl的血药 时间曲线用 3P97拟合。改良Ellman法测AChE活力。结果 PAM Cl在急性辛硫磷中毒大鼠和正常大鼠体内血药浓度经时过程均符合一室开放模型。与正常大鼠相比 ,PAM Cl在急性辛硫磷中毒大鼠体内血药最高峰浓度〔(2 2 85± 2 5 5 ) μg ml〕和血药 时间曲线下面积〔(13 0 4 0 2± 10 9 87) μg (min·ml)〕明显增高 (P <0 0 5 ) ,全身清除率〔(0 0 6± 0 0 1)L (min·kg)〕和中室表观分布容积〔(2 66± 0 3 7)L kg〕显著降低 (P <0 0 5 )。结论 PAM Cl在急性辛硫磷中毒大鼠体内的排泄较正常大鼠慢。 Objective To investigate pharmacokinetics of pralidoxime chloride (PAM-Cl) in acute phoxim-poisoning rats.Methods The rats were administered ip with 80 mg/kg of phoxim.The plasma concentration of PAM-Cl was determined by high performance liquid chromatography (HPLC).The profiles of PAM-Cl were analysed by 3P 97. Results The plasma concentration-time profiles of PAM-Cl in both acute phoxim-poisoning rats and normal rats are all accord with one compartment model.Compared with the parameters of normal rats, C _ max (22.85±2.55 μg/ml) and AUC 〔(1304.02±109.87) μg/(min·ml)〕 of PAM-Cl in poisoned rats were significantly increased ( P <0.05),TBCL 〔(0.06±0.01)L/(min\5kg)〕 and V_d 〔(2.66±0.37) L/kg〕 were remarkably decreased ( P <0.05). Conclusion The results imply that the excretion of PAM-Cl is slower in the acute phoxim-poisoning rats than that in the normal rats.
作者 琚志昌
出处 《卫生毒理学杂志》 CSCD 北大核心 2003年第2期90-93,共4页 Journal of Health Toxicology
基金 国家"十五"科技攻关课题 (2 0 0 1BA70 4B0 6)
关键词 辛硫磷中毒 氯解磷定 药物代谢动力学 乙酰胆碱酯酶 高效液相色谱法 Pralidoxime chloride Phoxim HPLC Pharmacokinetics
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