Oral heparin administration with a novel drug delivery agent (SNAC) in healthy volunteers and patients undergoing elective total hip arthroplasty.
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.
Berkowitz
S D
SD
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
Marder
V J
VJ
Kosutic
G
G
Baughman
R A
RA
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*
D002210:Caprylates; D004337:Drug Carriers; D065427:Factor Xa Inhibitors; C111140:N-(8-(2-hydroxybenzoyl)amino)caprylate; D006493:Heparin