Détail de la notice
Titre du Document
Inhibition of intestinal metabolism of the antiviral ester prodrug bis(POC)-PMPA by nature-identical fruit extracts as a strategy to enhance its oral absorption : An in vitro study
Auteur(s)
VAN GELDER J. ; ANNAERT P. ; NAESENS L. ; ...
Résumé
Purpose. To explore the usefulness of fruit extracts as enhancers of the oral absorption of esterase-sensitive prodrugs. Methods. Inhibition of esterase-mediated degradation by nature-identical fruit extracts was evaluated using 1) p-nitrophenylacetate (model substrate for esterase-activity) in rat intestinal homogenates and 2) bis(isopropyloxycarbonyloxymethyl)-(R)-9-[(2-phosphonomethoxy)propyl]adenine [bis(POC)-PMPA] (esterase-sensitive prodrug of the antiviral agent PMPA) in Caco-2 cell homogenates and in intestinal homogenates from rat, pig and man. Subsequently, transport of the ester prodrug was studied across Caco-2 monolayers in the presence or absence of fruit extracts. Results. In homogenates from rat ileum, the esterase activity could be reduced significantly by the inclusion of fruit extracts (1%): the initial enzymatic degradation of p-nitrophenylacetate was inhibited by 77% (strawberry), 16% (passion fruit) and 57% (banana). A similar inhibition of bis(POC)-PMPA metabolism by fruit extracts was observed in intestinal homogenates from several species and in homogenates from Caco-2 cells. Transport of total PMPA across Caco-2 monolayers was enhanced 3-fold by co-incubation with strawberry extract (1%). The fraction of intact prodrug appearing in the acceptor compartment increased from virtually zero to 67%. Conclusions. The results suggest that co-incubation with nature-identical fruit extracts might be useful as a strategy to enhance the transepithelial transport
Editeur
Springer
Identifiant
PMID : 10450927 ISSN : 0724-8741 CODEN : PHREEB
Source
Pharmaceutical research A. 1999, vol. 16, n° 7, pp. 1035-1040 [bibl. : 15 ref.]
Langue
Anglais
Pour les membres de la communauté du CNRS, ce document est autorisé à la reproduction à titre gratuit.
Pour les membres des communautés hors CNRS, la reproduction de ce document à titre onéreux sera fournie sous réserve d’autorisation du Centre Français d’exploitation du droit de Copie.

Pour bénéficier de nos services (strictement destinés aux membres de la communauté CNRS (Centre National de la Recherche Scientifique), de l'ESR français (Enseignement Supérieur et Recherche), et du secteur public français & étranger) :