title: A comparison of the pharmacodynamic behavior of branded and biosimilar enoxaparin in primates.
abstract: 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.
authors.affiliation: Cardiovascular Institute, Department of Thoracic & CV Surgery, Loyola University Chicago, Maywood, IL 60153, USA. wjeske@lumc.edu
authors.forename: Walter
authors.initials: W
authors.lastname: Jeske
authors.forename: Evangelos
authors.initials: E
authors.lastname: Litinas
authors.forename: Hussein
authors.initials: H
authors.lastname: Khan
authors.forename: Debra
authors.initials: D
authors.lastname: Hoppensteadt
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood; D016568:Drugs, Generic / Q000493:pharmacokinetics* / Q000494:pharmacology; D017984:Enoxaparin / Q000493:pharmacokinetics* / Q000494:pharmacology; D008253:Macaca mulatta
chemical_list: D000925:Anticoagulants; D019774:Blood Coagulation Factor Inhibitors; D016568:Drugs, Generic; D017984:Enoxaparin