| Title | Oral delivery of low-molecular-weight heparin using sodium caprate as absorption enhancer reaches therapeutic levels. | | Author(s) | Motlekar NA, Srivenugopal KS, Wachtel MS, Youan BB | | Institution | Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, 79106, USA. | | Source | J Drug Target 2005 Dec; 13(10):573-83. | | MeSH | Administration, Oral
Animals
Caco-2 Cells
Cell Membrane Permeability
Cell Survival
Decanoic Acids
Heparin, Low-Molecular-Weight
Humans
In Vitro
Intestinal Absorption
Intestines
Male
Rats
Rats, Sprague-Dawley
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Stomach
| | Abstract | The primary objective of this study was to evaluate sodium caprate as an oral penetration enhancer for low molecular weight heparin (LMWH), ardeparin. In vitro studies using Caco-2 cell monolayer indicated that 0.0625% of sodium caprate gave approximately 2-fold enhancement of ardeparin compared to negative control with almost 100% cell survival as evaluated by MTT cytotoxicity assay. In vivo studies in rats with ardeparin (1,200 IU/kg) and sodium caprate (100 mg/kg) led to a relative bioavailability of 27% with plasma anti-factor Xa levels within the therapeutic range (>0.2 IU/ml). Moreover, under these conditions, histological examination provided evidence that there was no damage to the gastrointestinal wall. Regional permeability studies using rat intestine indicated the colon as the region of maximum permeation. These results suggest that, at the dose administered, sodium caprate acts as a relatively safe and efficient absorption enhancer in the quest for alternatives for the oral delivery of LMWH. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 16390818 |
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