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Oral heparin administration with a novel drug delivery agent (SNAC) in healthy volunteers and patients undergoing elective total hip arthroplasty
Author(s) -
Berkowitz S. D.,
Marder V. J.,
Kosutic G.,
Baughman R. A.
Publication year - 2003
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1046/j.1538-7836.2003.00340.x
Subject(s) - medicine , heparin , regimen , anesthesia , arthroplasty , clinical trial , surgery
Summary. 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). Patients and 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. Conclusion : 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.