Sato J, Hamaguchi N, Doken K, Iwasa S, Ogawa Y, Toguchi H
DDS Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Biol Pharm Bull. 1994 Apr;17(4):535-8. doi: 10.1248/bpb.17.535.
We have investigated the pharmacokinetic alteration in rats of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2. Serum rIL-2 levels after the intravenous administration of the immune complex at a dose of 100 micrograms/rat as rIL-2 were significantly higher than those after intravenous administration of rIL-2 alone at the same dose. Pharmacokinetic analysis indicated that the distribution volume of rIL-2 decreased from 74.0 to 10.3 ml/rat, while the elimination rate of rIL-2 was little changed by immunocomplexing with the antibody. On the other hand, serum rIL-2 levels after the subcutaneous administration of the immune complex at a dose of 100 micrograms/rat as rIL-2 were sustained longer than those after the subcutaneous administration of rIL-2 alone at the same dose, and Tmax shifted from 0.83 to 3.0 h by immunocomplexing with the antibody. Pharmacokinetic analysis also revealed that the mean-residence-time of rIL-2 increased from 1.98 to 6.52 h, and the area-under-the curve of rIL-2 decreased slightly, from 834 to 548 ng.h/ml, by immunocomplexing with the antibody.
我们通过用抗重组白细胞介素-2（rIL-2）的单克隆抗体进行免疫复合，研究了rIL-2在大鼠体内的药代动力学变化。以100微克/大鼠的剂量静脉注射免疫复合物后，血清rIL-2水平（以rIL-2计）显著高于以相同剂量单独静脉注射rIL-2后的水平。药代动力学分析表明，rIL-2的分布容积从74.0降至10.3毫升/大鼠，而与抗体进行免疫复合后rIL-2的消除速率变化不大。另一方面，以100微克/大鼠的剂量皮下注射免疫复合物后，血清rIL-2水平（以rIL-2计）比以相同剂量单独皮下注射rIL-2后的水平维持时间更长，并且通过与抗体进行免疫复合，达峰时间从0.83小时变为3.0小时。药代动力学分析还显示，通过与抗体进行免疫复合，rIL-2的平均驻留时间从1.98小时增加到6.52小时，rIL-2的曲线下面积略有下降，从834降至548纳克·小时/毫升。
