A comparison of the pharmacodynamic behavior of branded and biosimilar enoxaparin in primates

Clin Appl Thromb Hemost. 2012 Jun;18(3):294-8. doi: 10.1177/1076029611432138. Epub 2012 Jan 23.


Pharmacodynamic behavior of branded and biosimilar enoxaparin was compared in a crossover study in primates. Blood samples collected at baseline and at 1, 4, 6, and 28 hours post-subcutaneous administration of Lovenox or Fibrinox were evaluated using clot-based and amidolytic assays. Anti-Xa levels following Fibrinox and Lovenox administration were not different. Anti-IIa levels were significantly higher in Lovenox-treated animals 1 to 6 hours post-administration. Higher drug levels were measured by Heptest in Fibrinox-treated animals from 4 to 6 hours. Pharmacokinetic differences were not observed using anti-Xa or Heptest assays. The area under the curve (anti-IIa) following Lovenox treatment was significantly larger than following Fibrinox treatment. When drug levels (anti-IIa) were plotted against anti-Xa or Heptest drug levels, a hysteretic relationship which was distinct for Fibrinox- and Lovenox-treated primates was observed suggesting a lack of bioequivalence for the low-molecular-weight heparin tested. In vivo behavior is an important consideration for defining pharmacoequivalence of complex biologic drugs.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anticoagulants / pharmacokinetics*
  • Anticoagulants / pharmacology
  • Blood Coagulation Factor Inhibitors / blood
  • Drugs, Generic / pharmacokinetics*
  • Drugs, Generic / pharmacology
  • Enoxaparin / pharmacokinetics*
  • Enoxaparin / pharmacology
  • Macaca mulatta


  • Anticoagulants
  • Blood Coagulation Factor Inhibitors
  • Drugs, Generic
  • Enoxaparin