Oral delivery of low-molecular-weight heparin using sodium caprate as absorption enhancer reaches therapeutic levels.
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.
Motlekar
Nusrat A
NA
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, 79106, USA.
Srivenugopal
Kalkunte S
KS
Wachtel
Mitchell S
MS
Youan
Bi-Botti C
BB
D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003652:Decanoic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000473:pathology
D003652:Decanoic Acids; D006495:Heparin, Low-Molecular-Weight; C031071:decanoic acid; C093450:ardeparin