Pharmacokinetics and tissue distribution of human recombinant interleukin-2 in mice. 1994

Z M Tang, and X W Liu, and L P Xu, and C W Shan, and Q S Song
Department of Pharmacology, Academy of Military Medical Sciences, Beijing, China.

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)

UI MeSH Term Description Entries
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D007457 Iodine Radioisotopes Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Radioisotopes, Iodine
D008297 Male Males
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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