title: Oral heparin administration with a novel drug delivery agent (SNAC) in healthy volunteers and patients undergoing elective total hip arthroplasty.
abstract: BACKGROUND
  Unfractionated heparin (UFH) is safe and effective for thromboprophylaxis, but its use is limited to parenteral administration. A novel drug delivery agent (SNAC) has been developed to accomplish the oral delivery of heparin.
  
  
  OBJECTIVE
  This report describes the foundation for dose selection and use of oral heparin/SNAC in patients undergoing elective total hip arthroplasty (THA).
  
  
  METHODS
  To develop a treatment regimen for clinical study, a multiple dose Phase I pharmacokinetic (PK) study in healthy volunteers compared oral heparin/SNAC (90 000 U heparin) with subcutaneous UFH (5000 U). On this basis, we carried out a double-blind, randomized, multicenter study comparing subcutaneous UFH (5000 U) with oral heparin/SNAC at either 60 000 or 90 000 U heparin in 123 patients undergoing elective THA. Patients received, postoperatively, one of the three treatments every 8 h for a total of 12 doses and were followed for 35 days post surgery.
  
  
  RESULTS
  In the Phase I study, anti-factor Xa activity peaked at 45-60 min following oral heparin/SNAC, returning to baseline at 4 h. RESULTS of the randomized trial in THA patients showed that venous thromboembolic events (n = 6), major bleeding events (n = 5) and need for transfusion (n = 23) were distributed evenly among the three treatment groups, UFH and both doses of oral heparin/SNAC.
  
  
  CONCLUSIONS
  This is the first demonstration that oral heparin/SNAC can be safely delivered to the postoperative THA patient, and provides the basis for a larger clinical trial to assess the prophylactic efficacy of heparin/SNAC.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Berkowitz
authors.forename: V J
authors.initials: VJ
authors.lastname: Marder
authors.forename: G
authors.initials: G
authors.lastname: Kosutic
authors.forename: R A
authors.initials: RA
authors.lastname: Baughman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D001803:Blood Transfusion; D002210:Caprylates; D004337:Drug Carriers; D065427:Factor Xa Inhibitors; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010599:Pharmacokinetics; D011182:Postoperative Care; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control*
chemical_list: D002210:Caprylates; D004337:Drug Carriers; D065427:Factor Xa Inhibitors; C111140:N-(8-(2-hydroxybenzoyl)amino)caprylate; D006493:Heparin