Oral delivery of anticoagulant doses of heparin. A randomized, double- blind, controlled study in humans

Circulation

Volumn 98, Issue 16, 1998, Pages 1610-1615

  Baughman, Robert A ^b   Kapoor, Shiv C ^a   Agarwal, Rajesh K ^b   Kisicki, James ^c   Catella Lawson, Francesca ^a   FitzGerald, Garret A ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b Emisphere Technologies Inc   (United States)

^c Harris Laboratories Inc Lincolnshire   (United States)

Author keywords

Anticoagulants; Heparin; Oral administration

Indexed keywords

ANTICOAGULANT AGENT; BLOOD CLOTTING FACTOR 10A; DRUG VEHICLE; HEPARIN; OCTANOIC ACID; PROTHROMBIN A; SODIUM N [8 (2 HYDROXYBENZOYL)AMINO]CAPRYLATE; THROMBOPLASTIN; UNCLASSIFIED DRUG;

ANTICOAGULATION; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG FORMULATION; DRUG MIXTURE; DRUG SAFETY; DRUG TOLERABILITY; GASTROINTESTINAL SYMPTOM; HEADACHE; HEMOSTASIS; HUMAN; HUMAN EXPERIMENT; NAUSEA; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; PARTIAL THROMBOPLASTIN TIME; PHARYNGITIS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; VOMITING;

EID: 0032552897     PISSN: 00097322     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.CIR.98.16.1610     Document Type: Article

References (35)

1. Hirsh J. Heparin. N Engl J Med. 1991;324:1565-1579.
2. Jaques LB. Heparins: anionic polyelectrolyte drugs. Pharmacolog Rev. 1980;31:100-166.
3. Jin L, Abrahams JP, Skinner R, Petitou M, Pike RN, Carrell RW. The anticoagulant activation of antithrombin by heparin. Proc Natl Acad Sci USA. 1997;94:14683-14688.
4. Hull R, Raskob G, Pineo G, Rosenbloom D, Evans W, Mallory T, Anquist K, Smith F, Hughes G, Green D, Elliott CG, Panju A, Brant R. A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Engl J Med. 1993;329:1370-1376.
5. Koopman MMW, Prandoni P, Piovella F, Ockelford PA, Brandjes DPM, van der Meer J, Gallus AS, Simonneau G, Chesterman CH, Prins MH, Bossuyt PMM, de Haes H, van den Belt AGM, Sagnard L, D'Azemar P, Buller HR, for the Tasman Study Group. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med. 1996;334:682-687.
6. Klein W, Buchwald A, Hillis SE, Monrad S, Sanz G, Graham A, Turpie G, van der Meer J, Olaisson E, Undeland S, Ludwig K, for the FRIC Investigators. Comparison of low-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease: Fragmin in Unstable Coronary Artery Disease Study (FRIC). Circulation. 1997;96:61-68.
7. FRISC Study Group. Low-molecular weight heparin during instability in coronary artery disease. Lancet. 1996;347:561-568.
8. Kay R, Wong KS, Yu YL, Chan YW, Tsoi TH, Ahuja AT, Chan FL, Fong KY, Law CB, Wong A, Woo J. Low-molecular-weight heparin for the treatment of acute ischemic stroke. N Engl J Med. 1995;333:1588-1593.
9. DalPozzo A, Acquasaliente M, Geron MR. New heparin complexes active by intestinal absorption, I: multiple ion pairs with basic organic compounds. Thromb Res. 1989;56:119-124.
10. White RH, Zhou H, Romano P, Mungall D. Changes in plasma warfarin levels and variations in steady-state prothrombin times. Clin Pharmacol Ther. 1995;58:588-593.
11. Merlini PA, Ardissino D, Bauer KA, Oltrona L, Pezzano A, Bottasso B, Rosenberg RD, Mannucci PM. Persistent thrombin generation during heparin therapy in patients with acute coronary syndromes. Arterioscler Thromb Vasc Biol. 1997;17:1325-1330.
12. Theroux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med. 1992;327:141-145.
13. Tidball CS, Lipman RI. Enhancement of jejunal absorption of heparinoid sodium ethylenediamine-tetraacetate in the dog. Proc Soc Exp Biol Med. 1962;111:713-715.
14. Sue TK, Jaques LB, Yuen E. Effects of acidity, cations, and alcoholic fractionation on absorption of heparin from the gastrointestinal tract. Can J Physiol Pharmacol. 1976;54:613-618.
15. Engel RH, Rigg GJ. Intestinal absorption of heparin facilitated by sulphate or sulfonated surfactant. Proc Soc Exp Bio Med. 1969;13: 706-710.
16. Guarani S, Ferrari W. Olive oil-provoked, bile-dependent absorption of heparin from the gastrointestinal tract in rats. Pharm Res Commun. 1985;17:685-694.
17. Uno M, Nagasaki T, Hiroshi I, Sakuragawa N. Oral administration of liposomally- entrapped heparin to beagle dogs. Chem Pharm Bull. 1982; 30:2245-2247.
18. Artmann C, Roding J, Ghyczy M, Pratzel HG. Liposomes from soya phospholipids as percutaneous drug carriers. Arzneimittelforschung. 1990;40:1365-1368.
19. Jacques LB, Hiebert LM, Wice SM. Evidence from endothelium of gastric absorption of heparin and of dextran sulfates 8000. J Lab Clin Med. 1991;117:122-130.
20. Leone-Bay A, Santiago N, Achan D, Chaudhary K, DeMorin F, Falzarano L, Haas S, Kalbag S, Kaplan D, Lercara C. O'Toole D, Rivera T, Rosado C, Sarubbi D, Vuocolo E, Wang NF, Milstein S, Baughman RA. N-acylated α-amino acids as novel oral delivery agents for proteins. J Med Chem. 1995;38:4263-4269.
21. Leone-Bay A, Ho K-K, Agarwal R, Baughman RA, Chaudhary K, DeMorin F, Genoble L, Lercara C, Milstein S, O'Toole D, Sarubbi D. Variano B, Paton D. 4-[4-(2 hydroxybenzoyl)amino]phenylbutyric acid as a novel delivery agent for recombinant human growth hormone. J Med Chem. 1996;39:2571-2576.
22. Brayden D, Creed E, O'Connell A, Leipold H, Agarwal R, Leone-Bay, A. Heparin absorption across the intestine: effects of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate in rat in situ intestinal installations and in caco-2 monolayers. Pharm Res. 1997;14:1772-1779.
23. Rivera T, Leone-Bay A, Paton D, Leipold H, Baughman R. Oral delivery of heparin in combination with sodium N-[8-(2-hydroxybenzoyl)amino]caprylate: pharmacology considerations. Pharm Res. 1997;14: 1830-1834.
24. Leone-Bay A, Paton DR, Variano B, Leipold H, Rivera T, Miura-Fraboni J, Baughman RA, Santiago N. Acylated non-α-amino acids as novel agents for the oral delivery of heparin sodium, USP. J Controlled Release. 1998;50:41-49.
25. Rivera T, Baughman RA, Rosado C, Kutzy T, Mayer E, and Leone-Bay A. Pharmacological profile of oral heparin using derivatized non-amino acids. Pharm Res. 1996;13:5-326. Abstract.
26. FitzGerald GA, Brash AK, Oates JA, Pedersen AK. Endogenous prostacyclin biosynthesis and platelet function during selective inhibition of thromboxane synthesis in man. J Clin Invest. 1983;72:1336-1343.
27. Novotny WF, Brown SG, Miletich JP, Rader DJ, Broze GJ Jr. Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples. Blood. 1991;78:387-393.
28. Alban S, Wolf H, Fareed J, Welzel D, Franz G. Correlation between LMWH anticoagulant activity and the TFPI plasma concentration in dependence on dosage and mode of application. Advances In Anticoagulant and Antithrombolic Drugs. Cambridge, Mass: IBC; 1996. Abstract.
29. Hull RD, Raskob GE, Hirsh J, Jay RM, Leclerc JR, Geerts WH, Rosenbloom D, Sackett DL, Anderson C, Harrison L, Gent M. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis. N Engl J Med. 1986;315:1109-1114.
30. Brill-Edwards P, Ginsberg JS, Johnston M, Hirsh J. Establishing a therapeutic range for heparin therapy. Ann Intern Med. 1993;119:104-109.
31. Cohen M, Demers C, Gurfinkel EP, Turpie AGG, Fromell GJ, Goodman S, Langer A, Califf RM, Box KAA, Premmerieur J, Bigonzi F, for the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med. 1997;337:447-452.
32. Lane DA, Adams L. Non-anti-coagulant uses of heparin. N Engl J Med. 1993:129-130 .
33. Eriksson BI, Wille-Jorgensen P, Kalebo P, Mouret P, Rosencher N, Bosch P, Baur M, Ekman S, Bach D, Lindbratt S, Close P. A comparison of recombinant hirudin with a low-molecular-weight heparin to prevent thromboembolic complications after total hip replacement. N Engl J Med. 1997;337:1329-1335.
34. Chesebro JH. Direct thrombin inhibition superior to heparin during and after thrombolysis: dose, duration, and drug. Circulation. 1997;96: 2118-2120.
35. White HD, Aylward PE, Frey MJ, Adgey AAJ, Nair R, Hillis WS, Shalev Y, Brown MA, French JK, Collins R, Maraganore J, Adelman B, for the Hirulog Early Reperfusion/Occlusion (HERO) Trial Investigators. Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO) Circulation. 1997;96:2155-2161.