Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of heparin as the most potent anticoagulant for the prevention of deep vein thrombosis and pulmonary embolism is nevertheless limited, because it is available to patients only by parenteral administration. Toward overcoming this limitation in the use of heparin, we have previously developed an orally active heparin-deoxycholic acid conjugate (LMWH-DOCA) in 10% DMSO formulation. The present study evaluates the anti-thrombogenic effect of this orally active LMWH-DOCA using a venous thrombosis animal model with Sprague-Dawley rats. When 5 mg/kg of LMWH-DOCA was orally administered in rats, the maximum anti-FXa activity in plasma was 0.35 +/- 0.02, and anti-FXa activity in plasma was maintained above 0.1 IU/ml [the minimum effective anti-FXa activity for the prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE)] for five hours. LMWH-DOCA (5 mg/kg, 430 IU/kg) that was orally administered reduced the thrombus formation by 56.3 +/- 19.8%;on the other hand, subcutaneously administered enoxaparin (100 IU/kg) reduced the thrombus formation by 36.4 +/- 14.5%. Also, LMWH-DOCA was effectively neutralized by protamine that was used as an antidote. Therefore, orally active LMWH-DOCA could be proposed as a new drug that is effective for the longterm prevention of DVT and PE.
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PMID:Prevention effect of orally active heparin derivative on deep vein thrombosis. 1689 57

The oral delivery of macromolecules is a topic of much interest as this would undoubtedly improve patient acceptance and compliance with chronic regimens. Heparin and insulin are perhaps among the first candidates that should be considered for oral macromolecule delivery systems. Heparin is the most potent anti-coagulant known for the prevention of deep vein thrombosis and pulmonary embolism, and an orally active heparin would undoubtedly effectively reduce chronic thrombotic events. Here, we report on the development of an orally administrable chemical conjugate of heparin and hydrophobic deoxycholic acid (DOCA), which we refer to as LHD. LHD was pre-formulated with dimethyl sulfoxide (DMSO) as solubilizer to further improve its oral bioavailability (9.1% in monkey). LHD was found to be absorbed mainly in the jejunum and ileum of the small intestine, although it is in the ileum that the absorption is most notable. From the mechanism studies of LHD absorption using Caco-2 cell monolayers for mimicking the intestine, we found that LHD highly permeated by passive diffusion through the transcellular route and its permeation was partially affected by bile acid transporters. This study demonstrates the feasibility of chemically modified heparin for long-term oral administration as an effective therapy for venous thromboembolism in clinical trials.
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PMID:Absorption study of deoxycholic acid-heparin conjugate as a new form of oral anti-coagulant. 1749 Jul 73