| Anticoagulant efficacy of solid oral formulations containing a new heparin derivative. | |
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MedLine Citation:
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PMID: 20349950 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The need for an efficacious and safe oral anticoagulant that does not require monitoring has been largely unmet. Many efforts have centered on preparing orally available heparin to improve patient compliance. In this study, novel orally active heparin derivatives (LHD), i.e. low molecular weight heparin (LMWH) conjugated with deoxycholic acid (DOCA), were evaluated in vitro and in vivo for their enhancement effect of oral heparin absorption. After oral administration of 10 mg/kg of water-soluble LHD, Ws-LHD1.5 showed optimum oral efficacy and its bioavailability was about 24% in rats. The oral absorption of LHD1.5 was also enhanced by several solubilizers, among which Poloxamer 407 provided the best results. When 5 mg/kg of LHD1.5 with Poloxamer 407 was orally administered to monkeys, the maximum anti-FXa activity in plasma was 0.26 +/- 0.04 IU/mL and its bioavailability was 17.4%. In a rat thrombosis model, 5 mg/kg of orally administered LHD1.5 formulated with Poloxamer reduced thrombus formation by 63.9 +/- 16.6%, which was higher than the efficacy of clinically used enoxaparin (49.4 +/- 17.8% at 100 IU/kg, sc). Considering the oral absorption efficacy and therapeutic effect, the conjugation ratio was optimized as about 1.5 molecules of DOCA per mole of heparin. Therefore, LHD1.5 with Poloxamer 407 can be further formulated as a solid oral anticoagulant drug. |
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Authors:
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Jin Woo Park; Ok Cheol Jeon; Sang Kyoon Kim; Taslim Ahmed Al-Hilal; Hyun Tae Moon; Choong Yong Kim; Youngro Byun |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular pharmaceutics Volume: 7 ISSN: 1543-8392 ISO Abbreviation: Mol. Pharm. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-07 Completed Date: 2010-09-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101197791 Medline TA: Mol Pharm Country: United States |
Other Details:
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Languages: eng Pagination: 836-43 Citation Subset: IM |
Affiliation:
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College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Animals Anticoagulants / administration & dosage*, chemistry, therapeutic use* Deoxycholic Acid / chemistry Heparin / administration & dosage*, chemistry, therapeutic use* Heparin, Low-Molecular-Weight / administration & dosage, chemistry, pharmacology Male Rats Rats, Sprague-Dawley Thrombosis / drug therapy |
| Chemical | |
Reg. No./Substance:
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0/Anticoagulants; 0/Heparin, Low-Molecular-Weight; 83-44-3/Deoxycholic Acid; 9005-49-6/Heparin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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