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Pharmacokinetics and tissue distribution of human recombinant interleukin-2 in mice

	author = {Zhong-ming Tang and Xiu-wen Liu and Lan-ping Xu and Chuan-wei Shan and Qian-sheng Song},
	title = {Pharmacokinetics and tissue distribution of human recombinant interleukin-2 in mice},
	journal = {Acta Pharmacologica Sinica},
	volume = {15},
	number = {1},
	year = {2016},
	keywords = {},
	abstract = {125I-labeled human recombinant interleukin-2 (125I-rIL-2) was prepared by iodogen method with rIL-2 and Na125I. 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 125I-rIL-2 fractions were selected for pharmacokinetic study, with a specific activity of 56 PBq.mol-1. Concentration-time curves after iv 75, 530, 603, and 6767 ng of 125I-rIL-2/mouse were fitted to a 3-compartment 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). Systematic clearances were independent of the dosages. SDS-PAGE of plasma and urine samples showed that radioactivities due to 125I-rIL-2 were 81 +/- 13% (n = 16) and 91 +/- 8% (n = 3, at 4 h), respectively. Levels of 125I-rIL-2 after im were lower than those after i.v., with bioavailability of 0.57. Time to peak concentration was about 1.1 h. The highest levels were seen at 15 min after i.v. in liver, bile and kidneys, the concentration gradients were blood > adrenals > plasma > lungs > thyroid > spleen > jejunum > mesenteric lymph nodes > jejunum contents > ovaries > heart > bladder > thymus > feces in colon > thigh skeletal muscle > testes > brain > fat. Peak concentration time in most tissues were found at 15 min, but at 4 h in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)},
	issn = {1745-7254},	url = {}