Pellets for oral administration of low-molecular-weight heparin

2009 ◽  
Vol 35 (12) ◽  
pp. 1503-1510 ◽  
Author(s):  
Julien Scala-Bertola ◽  
Jan Gajdziok ◽  
Miloslava Rabišková ◽  
François Bonneaux ◽  
Thomas Lecompte ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Oral Administration ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight

Pharmacokinetic evaluation of an oral tablet form of low-molecular-weight heparin and deoxycholic acid conjugate as a novel oral anticoagulant

2011 ◽  
Vol 105 (06) ◽  
pp. 1060-1071 ◽  
Author(s):  
Jin Woo Park ◽  
Ok Cheol Jeon ◽  
Sang Kyoon Kim ◽  
Taslim Al-Hilal ◽  
Kyung-Min Lim ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Oral Administration ◽  
Low Molecular Weight Heparin ◽  
Deoxycholic Acid ◽  
Oral Absorption ◽  
Metabolic Stability ◽  
Oral Dosage ◽  
Low Molecular Weight ◽  
Therapeutic Effects ◽  
Oral Tablet

SummaryThis study was designed to develop a solid oral dosage form of deoxycholic acid (DOCA)-conjugated low-molecular-weight heparin (LMWH) and to evaluate its oral absorption, distribution, and metabolic stability for the prospect of providing an orally bioavailable LMWH. The LMWH derivative (LHD) was synthesised and then formulated with solubilisers and other pharmaceutical excipients to form a solid tablet. Its absorption and distribution after oral administration were evaluated in mice, rats, and monkeys. The in vitro metabolic stability of LHD was examined by liver microsome assays. More than 80% of LHD was released from the tablet within 60 minutes, guaranteeing rapid tablet disintegration after oral administration. Oral bioavailability of LHD in mice, rats and monkeys were 16.1 ± 3.0, 15.6 ± 6.1, and 15.8 ± 2.5%, respectively. After the oral administration of 131I-tyramine-LHD, most of the absorbed drug remained in the blood circulation and was eliminated mainly through the kidneys. LHD was hardly metabolised by the liver microsomes and showed a stable metabolic pattern similar to that of LMWH. In a rat thrombosis model, 10 mg/kg of orally administered LHD reduced thrombus formation by 60.8%, which was comparable to the antithrombotic effect of the subcutaneously injected LMWH (100 IU/ kg). Solid tablets of LHD exhibited high oral absorption and statistically significant therapeutic effects in preventing venous thromboembolism. Accordingly, LHD tablets are expected to satisfy the unmet medical need for an oral heparin-based anticoagulant as an alternative to injectable heparin and oral warfarin.

Oral Administration of Low Molecular Weight Heparin Fractions in Rabbits

1985 ◽  
Vol 11 (03) ◽  
pp. 323-325 ◽  
Author(s):  
Christian Doutremepuich ◽  
Francis Toulemonde ◽  
Jean Lormeau
Keyword(s):  
Molecular Weight ◽  
Oral Administration ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Heparin Fractions

In vitroandin vivoinvestigation of low molecular weight heparin–alginate beads for oral administration

2013 ◽  
Vol 21 (4) ◽  
pp. 389-406 ◽  
Author(s):  
Canan İskenderoğlu ◽  
Füsun Acartürk ◽  
Deniz Erdoğan ◽  
Yeşim Bardakçı
Keyword(s):  
Molecular Weight ◽  
Oral Administration ◽  
Low Molecular Weight Heparin ◽  
Alginate Beads ◽  
Low Molecular Weight

Pellets for oral administration of low-molecular-weight heparin

2009 ◽  
Vol 00 (00) ◽  
pp. 090630072328049-8
Author(s):  
Julien Scala-Bertola ◽  
Jan Gajdziok ◽  
Miloslava Rabišková ◽  
François Bonneaux ◽  
Thomas Lecompte ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Oral Administration ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight

Anti Factor Xa Activity In Plasma Following Oral, Pulmonary, Subcutaneous And Intravenous Administration Of Cd5000 Low Molecular Weight Heparin And Commercial Heparin To Rats, Rabbits And Dogs

1981 ◽  
Author(s):  
L I Harrison ◽  
C R Kehe ◽  
R E Ober
Keyword(s):  
Molecular Weight ◽  
Oral Administration ◽  
Blood Coagulation ◽  
Intravenous Administration ◽  
Plasma Levels ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Dog Plasma ◽  
Antifactor Xa

CD5000 heparin (LMWH) is a low molecular weight heparin fraction, ave. mol wt. ∼ 5100. Plasma levels of antiFactor Xa activity (XaA) after iv, pulmonary, sc and oral administration of LMWH and commercial heparin (CH) were examined in rats, rabbits and dogs. Overall, LMWH maintained higher levels of XaA in plasma than did a similar mg dose of CH. When the heparins were given iv, plasma XaA after LMWH had a t1/2 ∼ 2X as long as that after CH. When similar mg doses were given sc, the average plasma XaA following LMWH was significantly higher than that following CH during 0-6 hrs postdose. When equal USP unit doses (four times as much LMWH on a mg basis) were administered into the lungs of dogs, LMWH showed plasma XaA significantly higher than after CH. LMWH also showed higher plasma XaA on oral administration of equal USP unit doses in rats, but the fraction of the dose absorbed and the plasma levels were low. About 4X as much LMWH on a mg basis as CH had to be given to achieve similar APTT values in dog plasma. LMWH may have significant therapeutic advantages in man if pharmacokinetic differences and different blood coagulation effects of the various mol wt. heparins described here in animals also occur in man. Studies in humans are planned.

Low-molecular-weight heparin in the prevention and treatment of thromboembolic disorders

1998 ◽  
Vol 1 (5) ◽  
pp. 166-174 ◽  
Author(s):  
Evelyn R Hermes De Santis ◽  
Betsy S Laumeister ◽  
Vidhu Bansal ◽  
Vandana Kataria ◽  
Preeti Loomba ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Prevention And Treatment
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