12.2.07

Darbepoetin alfa (Aranesp)

  • synthetic form of recombinant human erythropoietin (epoetin)
  • erythropoietin is an glycoprotein (protein with a bunch of sugars attached to it) hormone produced mostly by the kidney that stimulates erythropoiesis (production of red blood cells by the bone marrow)
  • epoetin and darbepoetin are manufactured using recombinant DNA technology:
    1. a gene encoding the protein/drug is inserted into a bunch of mammalian cells (usually Chinese Hamster Ovary cells)
    2. cells that begin to produce the drug are isolated and cultured in a bioreactor (placed in a controlled artificial environment and permitted to multiply)
    3. cultures of cells are processed to harvest the drug (see why they call it molecular farming?)
  • the gene encoding epoetin is identical to that which is found in humans, but the gene encoding darbepoetin has been tinkered with such that darbepoetin contains more sialic acid (a type of sugar) groups than epoetin - this modification increases its half-life three-fold and enhances its activity relative to epoetin
  • used to correct anemia (reduction in the amount of circulating red blood cells) associated with chronic kidney disease and cancer chemotherapy - these feature damage to the kidneys and bone marrow, respectively, which blunts the normal response of the body to anemia (increased release of erythropoietin from the kidney leading to increased red blood cell synthesis in the bone marrow)
  • has been abused by a number of athletes in endurance sports, particularly during the 2002 winter Olympics, as a variety of blood doping - increasing the number of red blood cells in order to enable the blood to carry more oxygen and thus enhance athletic performance
  • since it contains no components of human blood, may be okayed for use by those crazy Jehovah's Witnesses as a possible alternative to blood transfusion
  • excessive use can cause polycythemia (too many red blood cells to the point that they begin to significantly thicken the blood) - the heart has to work harder to pump the blood, increasing the risk of heart failure and other cardiovascular problems
Joy MS. Darbepoetin alfa: a novel erythropoiesis-stimulating protein. Ann Pharmacother. 2002 Jul-Aug;36(7-8):1183-92.
http://en.wikipedia.org/wiki/Darbepoetin_alfa

1 chemically inspired comments:

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