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Evaluation of the Oral Bioavailability of Low Molecular Weight Heparin Formulated With Glycyrrhetinic Acid as Permeation Enhancer.
Drug Dev Res 2006; 67(2):166-174DD

Abstract

Low molecular weight heparin (LMWH) is the agent of choice for anticoagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, its therapeutic use is limited due to poor oral bioavailability. The aim of this study was to investigate the oral delivery of LMWH, ardeparin formulated with 18-beta glycyrrhetinic acid (GA), as an alternative to currently used subcutaneous (sc) delivery. Drug transport through Caco-2 cell monolayers was monitored in the presence and absence of GA by scintillation counting and transepithelial electrical resistance. Regional permeability studies using rat intestine were performed using a modified Ussing chamber. Cell viability in the presence of various concentrations of enhancer was determined by MTT assay. The absorption of ardeparin after oral administration in rats was measured by an anti-factor Xa assay. Furthermore, the eventual mucosal epithelial damage was histologically evaluated. Higher ardeparin permeability (~7-fold) compared to control was observed in the presence of 0.02 % GA. Regional permeability studies indicated predominant absorption in the duodenal segment. Cell viability studies showed no significant cytotoxicity below 0.01 % GA. Ardeparin oral bioavailability was significantly increased (F(relative)/(S.C). = 13.3%) without causing any damage to the intestinal tissues. GA enhanced the oral absorption of ardeparin both in vitro and in vivo. The oral formulation of ardeparin with GA could be absorbed in the intestine. These results suggest that GA may be used as an absorption enhancer for the oral delivery of LMWH.

Authors

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Pub Type(s)

Journal Article

Language

eng

PubMed ID

17710191

Citation

Motlekar, Nusrat A., et al. "Evaluation of the Oral Bioavailability of Low Molecular Weight Heparin Formulated With Glycyrrhetinic Acid as Permeation Enhancer." Drug Development Research, vol. 67, no. 2, 2006, pp. 166-174.
Motlekar NA, Srivenugopal KS, Wachtel MS, et al. Evaluation of the Oral Bioavailability of Low Molecular Weight Heparin Formulated With Glycyrrhetinic Acid as Permeation Enhancer. Drug Dev Res. 2006;67(2):166-174.
Motlekar, N. A., Srivenugopal, K. S., Wachtel, M. S., & Youan, B. B. (2006). Evaluation of the Oral Bioavailability of Low Molecular Weight Heparin Formulated With Glycyrrhetinic Acid as Permeation Enhancer. Drug Development Research, 67(2), pp. 166-174.
Motlekar NA, et al. Evaluation of the Oral Bioavailability of Low Molecular Weight Heparin Formulated With Glycyrrhetinic Acid as Permeation Enhancer. Drug Dev Res. 2006;67(2):166-174. PubMed PMID: 17710191.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of the Oral Bioavailability of Low Molecular Weight Heparin Formulated With Glycyrrhetinic Acid as Permeation Enhancer. AU - Motlekar,Nusrat A, AU - Srivenugopal,Kalkunte S, AU - Wachtel,Mitchell S, AU - Youan,Bi-Botti C, PY - 2007/8/22/pubmed PY - 2007/8/22/medline PY - 2007/8/22/entrez SP - 166 EP - 174 JF - Drug development research JO - Drug Dev. Res. VL - 67 IS - 2 N2 - Low molecular weight heparin (LMWH) is the agent of choice for anticoagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, its therapeutic use is limited due to poor oral bioavailability. The aim of this study was to investigate the oral delivery of LMWH, ardeparin formulated with 18-beta glycyrrhetinic acid (GA), as an alternative to currently used subcutaneous (sc) delivery. Drug transport through Caco-2 cell monolayers was monitored in the presence and absence of GA by scintillation counting and transepithelial electrical resistance. Regional permeability studies using rat intestine were performed using a modified Ussing chamber. Cell viability in the presence of various concentrations of enhancer was determined by MTT assay. The absorption of ardeparin after oral administration in rats was measured by an anti-factor Xa assay. Furthermore, the eventual mucosal epithelial damage was histologically evaluated. Higher ardeparin permeability (~7-fold) compared to control was observed in the presence of 0.02 % GA. Regional permeability studies indicated predominant absorption in the duodenal segment. Cell viability studies showed no significant cytotoxicity below 0.01 % GA. Ardeparin oral bioavailability was significantly increased (F(relative)/(S.C). = 13.3%) without causing any damage to the intestinal tissues. GA enhanced the oral absorption of ardeparin both in vitro and in vivo. The oral formulation of ardeparin with GA could be absorbed in the intestine. These results suggest that GA may be used as an absorption enhancer for the oral delivery of LMWH. SN - 1098-2299 UR - https://www.unboundmedicine.com/medline/citation/17710191/Evaluation_of_the_Oral_Bioavailability_of_Low_Molecular_Weight_Heparin_Formulated_With_Glycyrrhetinic_Acid_as_Permeation_Enhancer L2 - https://doi.org/10.1002/ddr.20087 DB - PRIME DP - Unbound Medicine ER -