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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 the pharmacokinetics of recombinant human lymphotoxin α derivative (rhLTα-Da) in rats. Methods The total radioactivity of 125I-rhLTα-Da (125I-rhLTα-Da) was intravenously injected into 125I-rhLTα-Da. The total radioactivity in blood and urine samples at different time points was measured by isotope labeling. Trichloroacetic acid (TCA) precipitation method to detect radioactivity, pharmacokinetic parameters. Results The plasma concentration-time curves of 125Ⅰ-rhLTα-Da with different doses (25, 75 and 225μg / kg) were in accordance with the two-compartment model and the plasma half life (t1 / 2α) were 0.641,0.677 and 0.616 h (t1 / 2α corresponding to TCA precipitation method are 0.626,0.632 and 0.594 h), and the elimination half-lives (t1 / 2β) are 11.356, 13.373 and 16.033 h, respectively (t1 / 2β corresponding to TCA precipitation method is 11.329, 14.437 and 12.891 h ), Plasma concentration-time area under the curve (AUC) and dose was positively correlated. Conclusion The absorption, distribution and metabolism of rhLTα-Da in rats are in accordance with the characteristics of two-compartment model. The elimination of rhLTα-Da is slow but not easy to accumulate.