邻苯二甲酸酯在兔体内的毒代动力学

Toxicokinetics of Phthalates in Male Rabbits

目的研究邻苯二甲酸酯在兔体内的毒代动力学。方法选健康雄性家兔6只,恒速静脉滴注0.5g/kg的邻苯二甲酸二异辛酯(DEHP)或邻苯二甲酸二正丁酯(DBP),采用反相高效液相色谱法测定不同时间的血药浓度,用3P87实用药代动力学程序计算毒代动力学参数。结果DEHP和DBP分布相半衰期t1/2(α)分别为0.101、0.441h,消除相半衰期t1/2(β)分别为12.701、31.311h,清除率CLs分别为0.013、0.021g/(kg·h)。结论DEHP和DBP在兔体内的毒代动力学行为皆符合具一级消除的二室静脉恒速滴注模型,在兔体内的清除较快。

Objective To study the toxicokinetics of phthalates in male rabbits. Methods Concentrations of DEHP or DBP in plasma of 6 healthy male rabbits were determined by RP-HPLC after constant rate infusion of 0.5 g/kg DEHP or DBP(IV). The toxicokinetic parameters were computed by 3P87 program. Results The toxicokinetic model of DEHP and DBP were both first-order elimination and two-compartment model with constant rate infusion. The main toxicokinetic parameters of DEHP were as follows: distribution phose t1/2(α)=0.101 h; elimination phase t1/2(β)=12.701 h; CLs=0.013 g·kg-1·h-1. The main toxicokinetic parameters of DBP were as follows: t1/2(α)=0.441 h; t1/2(β)=31.311 h; CLs=0.021 g·kg-1·h-1. Conclusion DEHP and DBP were both first order elmination and two-compartment medol with constand rate intusion(IV). DEHP and DBP could be rapidly eliminated in male rabbits.