PHARMACOKINETICS AND TISSUE DISTRIBUTION OF HUMAN RECOMBINANT INTERLEUKIN-2 IN MICE

I-125-labeled human recombinant interleukin-2 (I-125-rIL-2) was prepar ed by iodogen method with rIL-2 and (NaI)-I-125. Product was purified by Sephacryl S-200 gel filtration. Eluate fractions were identified by SDS-PAGE and compared with standard rIL-2. Radioactive 95 % purified I-125-rIL-2 fractions were selected for pharmacokinetic study, with a specific activity of 56 PBq . mol-1. Concentration-time curves after i v 75, 530, 603, and 6767 ng of I-125-rIL-2/mouse were fitted to a 3-co mpartment model: with a fast distribution phase-T1/2 of 2 min, a slow distribution phase T1/2 of 30-120 min, and a terminal elimination T1/2 of 6 - 15 h. AUC was linearly related to the dosage (r = 0.9998). Sys tematic clearances were independent of the dosages. SDS-PAGE of plasma and urine samples showed that radioactivities due to I-125-rIL-2 were 81 +/- 13 % (n = 16) and 91 +/- 8 % (n = 3, at 4 h), respectively. Le vels of I-125-rIL-2 after im were lower than those after iv, with bioa vailability of 0.57. Time to peak concentration was about 1.1 h. The h ighest levels were seen at 15 min after- iv in liver, bile and kidneys , the concentration gradients were blood > adrenals > plasma > lungs > thyroid > spleen > jejunum > mesenteric lymph nodes > jejunum content s > ovaries > heart > bladder > thymus > feces in colon > thigh skelet al muscle > testes > brain > fat. Peak concentration time in most tiss ues were found at 15 min, but at 4 h in the feces. About 80 % of the i njected dose was excreted within the first 24 h, only 5 % excreted in the second day.