Pharmacokinetics of heparin and low molecular weight heparin fragment (Fragmin) in rabbits with impaired renal or metabolic clearance. 1987

M Palm, and C Mattsson
Kabi Vitrum Hematology, Department of Pharmacology, Stockholm, Sweden.

The kinetics and tissue distribution of 3H-heparin and a 3H-labelled low molecular weight heparin fragment were compared in normal rabbits as well as in rabbits with blocked renal function or reticuloendothelial system (RES). Radioactivity in plasma, urine, liver and kidneys, as well as anti-FXa activity in plasma were determined. The plasma elimination of heparin was, when compared to normal controls, prolonged both in rabbits with renal dysfunction as well as in rabbits with blocked RES, while renal dysfunction was the only parameter that significantly prolonged the plasma half-life of Fragmin. Studies on tissue distribution in normal rabbits revealed that about 60 per cent of the radioactive heparin dose accumulated in the liver and kidney three hours after the injection, whereas the corresponding value was less than 10 per cent for the Fragmin-derived radioactivity. The recovery of radioactivity in urine within three hours was 5 and 35 per cent of the dose, respectively, for 3H-heparin and 3H-Fragmin. It is concluded from the present study that the rapid plasma elimination of heparin in the rabbit (t1/2 = 17 minutes) is mainly due to a high tissue distribution (liver and kidney) while the plasma elimination of Fragmin (t1/2 = 28 minutes) is mainly caused by renal excretion.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D012157 Mononuclear Phagocyte System Mononuclear cells with pronounced phagocytic ability that are distributed extensively in lymphoid and other organs. It includes MACROPHAGES and their precursors; PHAGOCYTES; KUPFFER CELLS; HISTIOCYTES; DENDRITIC CELLS; LANGERHANS CELLS; and MICROGLIA. The term mononuclear phagocyte system has replaced the former reticuloendothelial system, which also included less active phagocytic cells such as fibroblasts and endothelial cells. (From Illustrated Dictionary of Immunology, 2d ed.) Reticuloendothelial System,Phagocyte System, Mononuclear,System, Mononuclear Phagocyte,System, Reticuloendothelial
D005260 Female Females
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006493 Heparin A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin
D006495 Heparin, Low-Molecular-Weight Heparin fractions with a molecular weight usually between 4000 and 6000 kD. These low-molecular-weight fractions are effective antithrombotic agents. Their administration reduces the risk of hemorrhage, they have a longer half-life, and their platelet interactions are reduced in comparison to unfractionated heparin. They also provide an effective prophylaxis against postoperative major pulmonary embolism. LMWH,Low-Molecular-Weight Heparin,Low Molecular Weight Heparin,Heparin, Low Molecular Weight
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

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