摘要
目的评价重组人淋巴毒素α衍生物(rhLTα-Da)在大鼠体内的药动学。方法大鼠静脉注射不同剂量125I标记重组人淋巴毒素α衍生物(125Ⅰ-rhLTα-Da)后,采用同位素示踪法检测不同时间点的血液和尿粪标本中的总放射性量,血浆样本同时以三氯乙酸(TCA)沉淀法检测放射性量,分析药动学参数。结果大鼠静脉注射不同剂量(25、75和225μg/kg)125Ⅰ-rhLTα-Da,其血药浓度-时间曲线符合二室模型特征,血浆分布半衰期(t1/2α)分别为0.641、0.677和0.616 h(TCA沉淀法对应的t1/2α为0.626、0.632和0.594 h),消除半衰期(t1/2β)分别为11.356、13.373和16.033 h(TCA沉淀法对应的t1/2β为11.329、14.437和12.891 h),血药浓度-时间曲线下面积(AUC)和剂量呈正相关。结论 rhLTα-Da在大鼠体内的吸收、分布和代谢符合二室模型特征,消除速度较慢,但不易蓄积。
Objective To evaluate pharmacokinetics profile of recombinant human lymphotoxin-α derivate（rhLTα-Da）in rats.Methods After intravenous injection with various dosage of 125I labeled rhLTα-Da（125I-rhLTα-Da）,blood samples,urine and fecal samples were collected at different time points.Gross radioactivity and trichloroacetic acid（TCA）precipitation method were used to detect the rhLTα-Da pharmacokinetics.Results As the dosages of rhLTα-Da 25,75 and 225 μg/kg were intravenously injected to rats,the concentration-time curve of rhLTα-Da in pharmacokinetics was conformed to be two-compartment model.Distribution half life（t1/2α）was 0.641,0.677 and 0.616 h（by TCA precipitation method its t1/2α was 0.626,0.632 and 0.594 h）.Elimination half life（t1/2β） was 11.356,13.373 and 16.033 h（by TCA precipitation method its t1/2β was 11.329,14.437 and 12.891 h）.Area under the plasma concentration time curve（AUC） was dose-dependent.Conclusion The absorption distribution and metabolism of rhLTα-Da were conformed to be two-compartment model.The exeretion was slow,but there is no accumulation.
出处
《世界临床药物》
CAS
2012年第11期662-665,共4页
World Clinical Drug
基金
上海市科学技术委员会资助项目(编号:08DZ2291400)
