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Of heparin

  Pharmacokinetics

  Absorption: The half-life of FRAGMIN has been shown to be 2 hours after intravenous injection and 3-4 hours after subcutaneous injection. The bioavailability after subcutaneous injection is approximately 90% and the pharmacokinetics are not dose-dependent. The plasma concentration of FRAGMIN following subcutaneous administration correlates directly with the administered dose and anti-Xa activity in plasma, as measured by the area under the activity curve. For the twice daily dosing regimen (100 IU/kg/12 hours) of FRAGMIN, the steady state level is attained after 2-4 s.c. injections (24-48 hours).

  Distribution: The volume of distribution was found to be approximately 3 litres.

  Animal studies using radioactively labelled drug have shown that the distribution of FRAGMIN is similar, whether the dose is administered intravenously or subcutaneously (i.v. or s.c.).

  Excretion: After 4 hours about 20% is seen in the urine, with most of the remainder found in the liver, GI tract and kidney. After 72 hours, 70% of a radioactive FRAGMIN dose has been excreted. Less FRAGMIN is found in the liver than standard heparin; the kidneys are the major site of FRAGMIN excretion (approximately 70% based on animal studies). Dalteparin sodium, in contrast to heparin, is not cleared by a saturable mechanism; low doses are expressed in plasma and increasing the dose does not modify its clearance.